m6A-centered Disease Response Information
General Information of the Disease (ID: M6ADIS0046)
Name |
Acute myeloid leukaemia
|
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---|---|---|---|---|---|
ICD |
ICD-11: 2A60
|
Full List of Target Gene(s) of This m6A-centered Disease Response
Aldehyde dehydrogenase 1A1 (ALDH1A1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | IGF2BP1 decreases leukemia cells' tumorigenicity, promotes myeloid differentiation, increases leukemia cell death, and sensitizes acute myeloid leukemia cells to chemotherapeutic drugs. IGF2BP1 affects proliferation and tumorigenic potential of leukemia cells through critical regulators of self-renewal HOXB4 and MYB and through regulation of expression of the aldehyde dehydrogenase, Aldehyde dehydrogenase 1A1 (ALDH1A1). | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) | READER | ||
Target Regulation | Up regulation | |||
In-vitro Model | MOLT-16 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_1424 |
Reh | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1650 | |
SKNO-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_2196 | |
Tanoue | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1852 | |
In-vivo Model | For the engraftment experiments, 1×103 1×106 cells were injected into tail veins of non-irradiated 6-10 week-old female mice in 100 uL of DPBS per mouse. No blinding or randomization was applied to mice experiments. Routinely, each in vivo experiment was performed with three technical replicates (three mice per group) and independently repeated two to three times for each cell line. | |||
Ankyrin repeat and SOCS box protein 2 (ASB2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [2] | |||
Response Summary | FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as Ankyrin repeat and SOCS box protein 2 (ASB2) and RARA by reducing m6A levels in these mRNA transcripts. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Responsed Drug | Tretinoin | Approved | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Cell Process | RNA stability | |||
RNA degradation (hsa03018) | ||||
In-vitro Model | K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 |
KOCL-48 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_6867 | |
Mono-Mac-6 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1426 | |
Apoptosis regulator Bcl-2 (BCL2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, Apoptosis regulator Bcl-2 (BCL2) and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | Apoptosis | hsa04210 | ||
Cell Process | Cell differentiation and apoptosis | |||
In-vitro Model | HSPC (Human hematopoietic stem cell) | |||
In-vivo Model | 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation. | |||
Cellular tumor antigen p53 (TP53/p53)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell cycle | hsa04110 | |||
Apoptosis | hsa04210 | |||
Cell Process | Cell apoptosis | |||
Cells in G3/M phase decreased | ||||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
MOLT-4 | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_0013 | |
Kasumi-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_0589 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
CCRF-CEM C7 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_6825 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 14 (METTL14) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell cycle | hsa04110 | |||
Apoptosis | hsa04210 | |||
Cell Process | Cell apoptosis | |||
Cells in G6/M phase decreased | ||||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
MOLT-4 | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_0013 | |
Kasumi-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_0589 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
CCRF-CEM C7 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_6825 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
Cyclin-dependent kinase inhibitor 1 (CDKN1A)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/Cyclin-dependent kinase inhibitor 1 (CDKN1A)), and downregulation of mdm2. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell cycle | hsa04110 | |||
Cell Process | Cell apoptosis | |||
Cells in G4/M phase decreased | ||||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
MOLT-4 | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_0013 | |
Kasumi-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_0589 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
CCRF-CEM C7 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_6825 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/Cyclin-dependent kinase inhibitor 1 (CDKN1A)), and downregulation of mdm2. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 14 (METTL14) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell cycle | hsa04110 | |||
Cell Process | Cell apoptosis | |||
Cells in G7/M phase decreased | ||||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
MOLT-4 | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_0013 | |
Kasumi-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_0589 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
CCRF-CEM C7 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_6825 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
DNA replication licensing factor MCM4 (MCM4)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [5] | |||
Response Summary | YTHDC1 knockdown has a strong inhibitory effect on proliferation of primary AML cells. YTHDC1 regulates leukemogenesis through DNA replication licensing factor MCM4 (MCM4), which is a critical regulator of DNA replication. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | YTH domain-containing protein 1 (YTHDC1) | READER | ||
Pathway Response | DNA replication | hsa03030 | ||
Cell Process | DNA replication | |||
E3 ubiquitin-protein ligase Mdm2 (Mdm2)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting E3 ubiquitin-protein ligase Mdm2 (Mdm2)/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell cycle | hsa04110 | |||
Cell Process | Cell apoptosis | |||
Cells in G2/M phase decreased | ||||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
MOLT-4 | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_0013 | |
Kasumi-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_0589 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
CCRF-CEM C7 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_6825 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting E3 ubiquitin-protein ligase Mdm2 (Mdm2)/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 14 (METTL14) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell cycle | hsa04110 | |||
Cell Process | Cell apoptosis | |||
Cells in G5/M phase decreased | ||||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
MOLT-4 | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_0013 | |
Kasumi-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_0589 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
CCRF-CEM C7 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_6825 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
eIF4E-binding protein 1 (4EBP1/EIF4EBP1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [6] | |||
Response Summary | Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell apoptosis | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
In-vivo Model | HL-60 cells (1 × 107) suspended in 0.1 ml PBS containing 50% Matrigel were subcutaneously injected into the flanks of the mice. When tumor sizes reached 200 mm3, the mice were randomly distributed into four groups with the indicated dosages of saline, cytarabine and BP alone or in combination. For BP injections, the solution was delivered intraperitoneally at 106 ug/kg body weight for the first 8 consecutive days. For cytarabine injections, the solution was delivered intraperitoneally at 100 mg/kg body weight three times (once every three days). The combination group was administered intraperitoneally three times (once every three days) with the same dosages as described above. The control group was treated with an equivalent amount of saline. | |||
Ephrin type-B receptor 2 (ERK/EPHB2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [7] | |||
Response Summary | FTO depended on its m6A RNA demethylase activity to activate PDGFRB/Ephrin type-B receptor 2 (ERK/EPHB2) signaling axis. FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated Acute myeloid leukemia(AML). | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
Pathway Response | Apoptosis | hsa04210 | ||
Cell Process | Cell apoptosis | |||
In-vitro Model | OCI-AML-3 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1844 |
OCI-AML-2 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1619 | |
Homeobox protein Hox-B4 (HOXB4)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | IGF2BP1 decreases leukemia cells' tumorigenicity, promotes myeloid differentiation, increases leukemia cell death, and sensitizes acute myeloid leukemia cells to chemotherapeutic drugs. IGF2BP1 affects proliferation and tumorigenic potential of leukemia cells through critical regulators of self-renewal Homeobox protein Hox-B4 (HOXB4) and MYB and through regulation of expression of the aldehyde dehydrogenase, ALDH1A1. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) | READER | ||
Target Regulation | Up regulation | |||
In-vitro Model | MOLT-16 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_1424 |
Reh | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1650 | |
SKNO-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_2196 | |
Tanoue | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1852 | |
In-vivo Model | For the engraftment experiments, 1×103 1×106 cells were injected into tail veins of non-irradiated 6-10 week-old female mice in 100 uL of DPBS per mouse. No blinding or randomization was applied to mice experiments. Routinely, each in vivo experiment was performed with three technical replicates (three mice per group) and independently repeated two to three times for each cell line. | |||
Isocitrate dehydrogenase [NADP] cytoplasmic (IDH/IDH1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [8] | |||
Response Summary | 1) Isocitrate dehydrogenase [NADP] cytoplasmic (IDH/IDH1) mutant cells, likely via a D2-HG-mediated competitive inhibition of the Alpha-KG-dependent RNA demethylase FTO, display significantly elevated RNA methylation; 2) Deregulated RNA methylation should be considered part of the pathogenesis of IDH-mutant tumors, which alongside with the well-characterized DNA and histone disturbances defines a "hypermethylation triad"; 3) the effects of FTO expression on AML pathogenesis need to be interpreted in the context of IDH1/2 mutation since in this setting FTO activity is probably low, irrespective of its expression level. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Cell Process | Glutamine metabolism | |||
In-vitro Model | HEK293T | Normal | Homo sapiens | CVCL_0063 |
Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4)
In total 7 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Experiment 5 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Experiment 6 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Experiment 7 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
Cell Process | Immune Evasion | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
Mutated in multiple advanced cancers 1 (PTEN)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and Mutated in multiple advanced cancers 1 (PTEN) mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell differentiation and apoptosis | |||
Apoptosis (hsa04210) | ||||
In-vitro Model | HSPC (Human hematopoietic stem cell) | |||
In-vivo Model | 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation. | |||
Myc proto-oncogene protein (MYC)
In total 4 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [10] | |||
Response Summary | WTAP made acute myeloid leukemia cells resistant to daunorubicin. In further investigations, m6A methylation level was downregulated when knocking down WTAP, and Myc proto-oncogene protein (MYC) was upregulated due to the decreased m6A methylation of MYC mRNA. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Responsed Drug | Daunorubicin | Approved | ||
Target Regulator | Wilms tumor 1-associating protein (WTAP) | WRITER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell cycle | |||
Cell proliferation | ||||
Cell apoptosis | ||||
In-vitro Model | K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of Myc proto-oncogene protein (MYC), BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell differentiation and apoptosis | |||
Apoptosis (hsa04210) | ||||
In-vitro Model | HSPC (Human hematopoietic stem cell) | |||
In-vivo Model | 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation. | |||
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene | [11] | |||
Response Summary | METTL14 in normal myelopoiesis and AML pathogenesis, as featured by blocking myeloid differentiation and promoting self-renewal of normal HSPCs and LSCs/LICs. METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and Myc proto-oncogene protein (MYC)) through m6A modification, while the protein itself is negatively regulated by SPI1. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 14 (METTL14) | WRITER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell survival/proliferation | |||
In-vitro Model | HEK293T | Normal | Homo sapiens | CVCL_0063 |
HSPC (Human hematopoietic stem cell) | ||||
MNC (Cord blood pluripotent stem cells) | ||||
OP9 | Normal | Mus musculus | CVCL_4398 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | Lin- HSPCs were purified from BM of wildtype mice and 0.1×106 cells were seeded in 2 mL OP9 medium onto the OP9 cells with the addition of 10 ng/mL mouse IL-3, 10 ng/mL human IL-6, 10 ng/mL mouse IL-7, 10 ng/mL mouse Flt-3L, and 50 ng/mL mouse stem cell factor (SCF). | |||
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene | [12] | |||
Response Summary | METTL3 level was slightly increased in AML-M5 patients,and its expression was significantly higher in immature cells than in mature monocytes.METTL3 acts as an oncogene in MOLM13 cells by upregulating Myc proto-oncogene protein (MYC) expression. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell proliferation | |||
In-vitro Model | MOLM-13 | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 |
Nucleophosmin (NPM1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [7] | |||
Response Summary | FTO depended on its m6A RNA demethylase activity to activate PDGFRB/ERK signaling axis. FTO-mediated m6A demethylation plays an oncogenic role in Nucleophosmin (NPM1)-mutated Acute myeloid leukemia(AML). | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
In-vitro Model | OCI-AML-3 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1844 |
OCI-AML-2 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1619 | |
Platelet-derived growth factor receptor beta (PDGFRB)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [7] | |||
Response Summary | FTO depended on its m6A RNA demethylase activity to activate Platelet-derived growth factor receptor beta (PDGFRB)/ERK signaling axis. FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated Acute myeloid leukemia(AML). | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell apoptosis | |||
In-vitro Model | OCI-AML-3 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1844 |
OCI-AML-2 | Adult acute myeloid leukemia | Homo sapiens | CVCL_1619 | |
Protein RCC2 (RCC2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [13] | |||
Response Summary | IGF2BP3 is required for maintaining AML cell survival in an m6A-dependent manner, and knockdown of IGF2BP3 dramatically suppresses the apoptosis, reduces the proliferation, and impairs the leukemic capacity of AML cells in vitro and in vivo.IGF2BP3 interacts with Protein RCC2 (RCC2) mRNA and stabilizes the expression of m6A-modified RNA. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) | READER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell apoptosis | |||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
SUP-B15 | B-lymphoblastic leukemia | Homo sapiens | CVCL_0103 | |
KG-1 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
RAC-alpha serine/threonine-protein kinase (AKT1)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | Apoptosis | hsa04210 | ||
Cell Process | Cell differentiation and apoptosis | |||
In-vitro Model | HSPC (Human hematopoietic stem cell) | |||
In-vivo Model | 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation. | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [14] | |||
Response Summary | Downregulated METTL3 expression in AML-MSCs induced an increase in RAC-alpha serine/threonine-protein kinase (AKT1) protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in acute myeloid leukaemia (AML) cells. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Pathway Response | PI3K-Akt signaling pathway | hsa04151 | ||
Cell Process | Adipogenesis | |||
In-vitro Model | HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Retinoic acid receptor alpha (RARA)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [2] | |||
Response Summary | FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and Retinoic acid receptor alpha (RARA) by reducing m6A levels in these mRNA transcripts. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Responsed Drug | Tretinoin | Approved | ||
Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
Target Regulation | Down regulation | |||
Cell Process | RNA stability | |||
RNA degradation (hsa03018) | ||||
In-vitro Model | K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 |
KOCL-48 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_6867 | |
Mono-Mac-6 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1426 | |
Target of rapamycin complex subunit LST8 (MLST8)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [6] | |||
Response Summary | Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell apoptosis | |||
In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
HEK293T | Normal | Homo sapiens | CVCL_0063 | |
In-vivo Model | HL-60 cells (1 × 107) suspended in 0.1 ml PBS containing 50% Matrigel were subcutaneously injected into the flanks of the mice. When tumor sizes reached 200 mm3, the mice were randomly distributed into four groups with the indicated dosages of saline, cytarabine and BP alone or in combination. For BP injections, the solution was delivered intraperitoneally at 106 ug/kg body weight for the first 8 consecutive days. For cytarabine injections, the solution was delivered intraperitoneally at 100 mg/kg body weight three times (once every three days). The combination group was administered intraperitoneally three times (once every three days) with the same dosages as described above. The control group was treated with an equivalent amount of saline. | |||
Transcription factor Sp1 (SP1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [15] | |||
Response Summary | Genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Two genes expressing the transcription factors Transcription factor Sp1 (SP1) and SP2, which have promoters occupied by METTL3. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Cell Process | Cell cycle | |||
In-vitro Model | EoL-1 | Chronic eosinophilic leukemia | Homo sapiens | CVCL_0258 |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
Jurkat | T acute lymphoblastic leukemia | Homo sapiens | CVCL_0065 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
KG-1 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | |
Loucy | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_1380 | |
MOLM-13 | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
NOMO-1 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1609 | |
RN2c (Acute myeloid leukemia cell line) | ||||
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
In-vivo Model | Performed an ex vivo genome wide CRISPR dropout screen (Screen 1) using Cas9-expressing mouse primary leukaemia cells driven by an MLL-AF9 fusion gene and a FLT3 internal tandem duplication. | |||
Transcription factor Sp2 (SP2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [15] | |||
Response Summary | Genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Two genes expressing the transcription factors SP1 and Transcription factor Sp2 (SP2), which have promoters occupied by METTL3. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Cell Process | Cell cycle | |||
In-vitro Model | EoL-1 | Chronic eosinophilic leukemia | Homo sapiens | CVCL_0258 |
HEL | Erythroleukemia | Homo sapiens | CVCL_0001 | |
HL-60 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
Jurkat | T acute lymphoblastic leukemia | Homo sapiens | CVCL_0065 | |
K-562 | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | |
KG-1 | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | |
Loucy | Adult T acute lymphoblastic leukemia | Homo sapiens | CVCL_1380 | |
MOLM-13 | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
NOMO-1 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1609 | |
RN2c (Acute myeloid leukemia cell line) | ||||
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
In-vivo Model | Performed an ex vivo genome wide CRISPR dropout screen (Screen 1) using Cas9-expressing mouse primary leukaemia cells driven by an MLL-AF9 fusion gene and a FLT3 internal tandem duplication. | |||
Transcriptional activator Myb (MYB)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [11] | |||
Response Summary | METTL14 in normal myelopoiesis and AML pathogenesis, as featured by blocking myeloid differentiation and promoting self-renewal of normal HSPCs and LSCs/LICs. METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., Transcriptional activator Myb (MYB) and MYC) through m6A modification, while the protein itself is negatively regulated by SPI1. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Methyltransferase-like 14 (METTL14) | WRITER | ||
Target Regulation | Up regulation | |||
Cell Process | Cell survival/proliferation | |||
In-vitro Model | HEK293T | Normal | Homo sapiens | CVCL_0063 |
HSPC (Human hematopoietic stem cell) | ||||
MNC (Cord blood pluripotent stem cells) | ||||
OP9 | Normal | Mus musculus | CVCL_4398 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | Lin- HSPCs were purified from BM of wildtype mice and 0.1×106 cells were seeded in 2 mL OP9 medium onto the OP9 cells with the addition of 10 ng/mL mouse IL-3, 10 ng/mL human IL-6, 10 ng/mL mouse IL-7, 10 ng/mL mouse Flt-3L, and 50 ng/mL mouse stem cell factor (SCF). | |||
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | IGF2BP1 decreases leukemia cells' tumorigenicity, promotes myeloid differentiation, increases leukemia cell death, and sensitizes acute myeloid leukemia cells to chemotherapeutic drugs. IGF2BP1 affects proliferation and tumorigenic potential of leukemia cells through critical regulators of self-renewal HOXB4 and Transcriptional activator Myb (MYB) and through regulation of expression of the aldehyde dehydrogenase, ALDH1A1. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) | READER | ||
Target Regulation | Up regulation | |||
In-vitro Model | MOLT-16 | T acute lymphoblastic leukemia | Homo sapiens | CVCL_1424 |
Reh | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1650 | |
SKNO-1 | Myeloid leukemia with maturation | Homo sapiens | CVCL_2196 | |
Tanoue | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1852 | |
In-vivo Model | For the engraftment experiments, 1×103 1×106 cells were injected into tail veins of non-irradiated 6-10 week-old female mice in 100 uL of DPBS per mouse. No blinding or randomization was applied to mice experiments. Routinely, each in vivo experiment was performed with three technical replicates (three mice per group) and independently repeated two to three times for each cell line. | |||
Transforming acidic coiled-coil-containing protein 3 (TACC3)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [16] | |||
Response Summary | ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Up regulation | |||
Pathway Response | Signaling pathways regulating pluripotency of stem cells | hsa04550 | ||
Cell Process | Self-renewal | |||
In-vitro Model | HEK293T | Normal | Homo sapiens | CVCL_0063 |
MOLM-13 | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | |
Mono-Mac-6 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1426 | |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
NB4 | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
NOMO-1 | Adult acute monocytic leukemia | Homo sapiens | CVCL_1609 | |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
In-vivo Model | gRNA and Cas9 mRNA were mixed at concentration of 50 and 100 ng/ul, respectively, and injected to the cytoplasm of one-cell-stage embryos of C57BL/6 genetic background. | |||
Tyrosine-protein kinase receptor UFO (AXL)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [17] | |||
Response Summary | Expression of m6A demethylase ALKBH5 is regulated by chromatin state alteration during leukemogenesis of human acute myeloid leukemia (AML), and ALKBH5 is required for maintaining leukemia stem cell (LSC) function but is dispensable for normal hematopoiesis. ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | ||
Target Regulation | Down regulation | |||
Pathway Response | PI3K-Akt signaling pathway | hsa04151 | ||
Cell Process | mRNA stability | |||
In-vitro Model | MOLM-13 | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 |
MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | |
THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
In-vivo Model | Congenic recipient mice (CD45.2) at 8-10 weeks old were used for AML transplantation, and CD45.1 recipients at 8-10 weeks old were used for normal hematopoietic transplantation assays. | |||
Tnfrsf2
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [18] | |||
Response Summary | Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). YTHDF2 decreases the half-life of diverse m6A transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis. | |||
Responsed Disease | Acute myeloid leukaemia [ICD-11: 2A60] | |||
Target Regulator | YTH domain-containing family protein 2 (YTHDF2) | READER | ||
Target Regulation | Down regulation | |||
Pathway Response | Signaling pathways regulating pluripotency of stem cells | hsa04550 | ||
Cell Process | mRNA decay | |||
In-vitro Model | THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
In-vivo Model | THP-1 cells transduced with CTL or KD lentiviruses were tail vein injected into non-irradiated 12 week-old female non-obese diabetic (NOD)/LtSz-severe combined immune-deficiency (SCID) IL-2Rγcnull (NSG) mice (1x106 cells per 200 uL per mouse). | |||
References