Name	Acute myeloid leukaemia
ICD	ICD-11: 2A60

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	Regulator Info
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.

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	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
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

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	Regulator Info
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.

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	Regulator Info
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	Regulator Info
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

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	Regulator Info
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	Regulator Info
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

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	Regulator Info
Pathway Response	DNA replication			hsa03030
Cell Process	DNA replication

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	Regulator Info
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	Regulator Info
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

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	Regulator Info
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.

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	Regulator Info
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

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	Regulator Info
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.

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	Regulator Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063

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	Regulator Info
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	Regulator Info
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	Regulator Info
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	Regulator Info
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	Regulator Info
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	Regulator Info
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	Regulator Info
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.

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	Regulator Info
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.

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	Drug Info
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
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	Regulator Info
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	Regulator Info
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	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119

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	Regulator Info
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

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	Regulator Info
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

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	Regulator Info
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

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	Regulator Info
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	Regulator Info
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

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	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
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

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	Regulator Info
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.

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	Regulator Info
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.

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	Regulator Info
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.

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	Regulator Info
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	Regulator Info
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.

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	Regulator Info
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.

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	Regulator Info
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.

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	Regulator Info
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).

Ref 1	RNA-binding protein IGF2BP1 maintains leukemia stem cell properties by regulating HOXB4, MYB, and ALDH1A1. Leukemia. 2020 May;34(5):1354-1363. doi: 10.1038/s41375-019-0656-9. Epub 2019 Nov 25.
Ref 2	FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N(6)-Methyladenosine RNA Demethylase. Cancer Cell. 2017 Jan 9;31(1):127-141. doi: 10.1016/j.ccell.2016.11.017. Epub 2016 Dec 22.
Ref 3	The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017 Nov;23(11):1369-1376. doi: 10.1038/nm.4416. Epub 2017 Sep 18.
Ref 4	The m(6)A RNA methyltransferase METTL3/METTL14 promotes leukemogenesis through the mdm2/p53 pathway in acute myeloid leukemia. J Cancer. 2022 Jan 4;13(3):1019-1030. doi: 10.7150/jca.60381. eCollection 2022.
Ref 5	A critical role of nuclear m6A reader YTHDC1 in leukemogenesis by regulating MCM complex-mediated DNA replication. Blood. 2021 Dec 30;138(26):2838-2852. doi: 10.1182/blood.2021011707.
Ref 6	Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m(6)A demethylation of EIF4EBP1 and MLST8 mRNA. Cell Oncol (Dordr). 2022 Jun;45(3):355-365. doi: 10.1007/s13402-022-00666-9. Epub 2022 May 17.
Ref 7	Mutant NPM1-Regulated FTO-Mediated m(6)A Demethylation Promotes Leukemic Cell Survival via PDGFRB/ERK Signaling Axis. Front Oncol. 2022 Feb 8;12:817584. doi: 10.3389/fonc.2022.817584. eCollection 2022.
Ref 8	IDH Mutation, Competitive Inhibition of FTO, and RNA Methylation. Cancer Cell. 2017 May 8;31(5):619-620. doi: 10.1016/j.ccell.2017.04.001.
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