Name	Multiple myeloma
ICD	ICD-11: 2A83

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO significantly promotes MM cell proliferation, migration, and invasion by targeting Heat shock factor protein 1 (HSF1)/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NCG mice.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug	Bortezomib		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	MM1.R	Plasma cell myeloma	Homo sapiens	CVCL_8794
In-vivo Model	A total of 3×106 RPMI8226/MM1R-Luc cells were intravenously injected into NCG mice to establish a disseminated human MM xenograft model. The in vivo antitumor effect of the FTO inhibitor MA2 combined with or without the first-line chemotherapeutic agent BTZ was evaluated as follows: 3 days post xenotransplantation, MA2 (20 mg/kg), or vehicle control was injected intraperitoneally (i.p.) daily for 10 days, and BTZ was injected intraperitoneally on days 1, 4, 8, and 11. Mouse serum was collected at specified time points during the treatment, and the tumor burden was monitored by detecting myeloma cell-secreted Lambda light chains via a Human Lambda ELISA Kit (Bethyl Laboratories, No. E88-116). Tumor development was monitored weekly after treatment with an in vivo imaging system (IVIS, SI Imaging, Lago, and LagoX). Luciferin (150 mg/kg, YEASEN, Shanghai, China) was injected intraperitoneally into the mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-dependent effect of HNRNPA2B1 on regulating AKT signaling pathway and the correlation between HNRNPA2B1 and multiple myeloma cell growth. HNRNPA2B1 recognized the m6A sites of Interleukin enhancer-binding factor 3 (ILF3) and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Inhibiting ALKBH5 in Multiple Myeloma cells increased Protein salvador homolog 1 (SAV1) m6A levels, decreased SAV1 mRNA stability and expression, suppressed the stem cell related HIPPO-pathway signalling and ultimately activates the downstream effector YAP, exerting an anti-myeloma effect.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation
	Cell invasion
In-vitro Model	U266 (Human multiple myeloma cells)
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	ARH-77	Human leukemia tumor	Homo sapiens	CVCL_1072

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-dependent effect of HNRNPA2B1 on regulating AKT signaling pathway and the correlation between HNRNPA2B1 and multiple myeloma cell growth. HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while RAC-gamma serine/threonine-protein kinase (AKT3) downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	The analyses of m6A-RIP-seq and RIP-PCR indicated that Signal transducer and activator of transcription 5A (STAT5A) was the downstream target of YTHDF2, which was binding to the m6A modification site of STAT5A to promote its mRNA degradation. ChIP-seq and PCR assays revealed that STAT5A suppressed multiple myelomacell proliferation by occupying the transcription site of MAP2K2 to decrease ERK phosphorylation.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	FTO promotes Bortezomib resistance via m6A-dependent destabilization of Superoxide dismutase [Mn], mitochondrial (SOD2) expression in multiple myeloma.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug	Bortezomib		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	ALKBH5 promoted multiple myeloma cell growth and survival through TNF receptor-associated factor 1 (TRAF1)-mediated activation of NF-Kappa-B and MAPK signaling pathways.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell apoptosis
	RNA stability
In-vitro Model	CAG	Plasma cell myeloma	Homo sapiens	CVCL_D569
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	U266 (Human multiple myeloma cells)
In-vivo Model	5 × 105 selected cells were injected via the tail vein into 4- to 5-week-old NCG mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of Transcriptional repressor protein YY1 (YY1) mRNA and the maturation of primary-miR-27a-3p in vitro and in vivo.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	U266 (Human multiple myeloma cells)
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	MM1.S	Plasma cell myeloma	Homo sapiens	CVCL_8792
In-vivo Model	BALB/C nude mice (5 weeks old, weighing 18-22 g) were fed in specific pathogen-free facilities and subcutaneously inoculated with U266 cells (1 × 106). The mice were randomly divided into 3 groups with 6 mice per group, when the tumor was measurable. Then, miR-27a-3p mimic or sh-METTL3 was injected intratumorally at an interval of 4 days a total of 4 times. Tumor volume was measured using a digital caliper every week and calculated using the formula V = 1/2 (width2 × length).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of YY1 mRNA and the maturation of pri-miR-27 in vitro and in vivo.
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	U266 (Human multiple myeloma cells)
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	MM1.S	Plasma cell myeloma	Homo sapiens	CVCL_8792
In-vivo Model	BALB/C nude mice (5 weeks old, weighing 18-22 g) were fed in specific pathogen-free facilities and subcutaneously inoculated with U266 cells (1 × 106). The mice were randomly divided into 3 groups with 6 mice per group, when the tumor was measurable. Then, miR-27a-3p mimic or sh-METTL3 was injected intratumorally at an interval of 4 days a total of 4 times. Tumor volume was measured using a digital caliper every week and calculated using the formula V = 1/2 (width2 × length).

Ref 1	FTO promotes multiple myeloma progression by posttranscriptional activation of HSF1 in an m(6)A-YTHDF2-dependent manner. Mol Ther. 2022 Mar 2;30(3):1104-1118. doi: 10.1016/j.ymthe.2021.12.012. Epub 2021 Dec 13.
Ref 2	HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA. J Hematol Oncol. 2021 Apr 1;14(1):54. doi: 10.1186/s13045-021-01066-6.
Ref 3	ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing m(6)A-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype. Int J Biol Sci. 2022 Mar 6;18(6):2235-2248. doi: 10.7150/ijbs.64943. eCollection 2022.
Ref 4	YTHDF2 promotes multiple myeloma cell proliferation via STAT5A/MAP2K2/p-ERK axis. Oncogene. 2022 Mar;41(10):1482-1491. doi: 10.1038/s41388-022-02191-3. Epub 2022 Jan 24.
Ref 5	FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma. Cancer Gene Ther. 2022 Feb 10. doi: 10.1038/s41417-022-00429-6. Online ahead of print.
Ref 6	RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-KappaB and MAPK signaling pathways. Oncogene. 2022 Jan;41(3):400-413. doi: 10.1038/s41388-021-02095-8. Epub 2021 Nov 10.
Ref 7	METTL3 facilitates multiple myeloma tumorigenesis by enhancing YY1 stability and pri-microRNA-27 maturation in m(6)A-dependent manner. Cell Biol Toxicol. 2022 Jan 17. doi: 10.1007/s10565-021-09690-1. Online ahead of print.