Details of Disease

General Information of Disease (ID: DIS5VZDR)

• Disease Name: Childhood acute megakaryoblastic leukemia
• Definition: An acute megakaryocytic leukemia that is characterized by fusion oncogenes involving transcriptional regulators in childhood.
• Disease Hierarchy:
  DIS0JX3M: Acute megakaryoblastic leukemia
  DIS5VZDR: Childhood acute megakaryoblastic leukemia
• Disease Identifiers:
  MONDO ID: MONDO_0850267
  UMLS CUI: C0279650
  MedGen ID: 79023

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Bevacizumab	DMSD1UN	Approved	Monoclonal antibody	[1]
Cytarabine	DMZD5QR	Approved	Small molecular drug	[2]
Idarubicin	DMM0XGL	Approved	Small molecular drug	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KDM5A	TTIG67W	Limited	Biomarker	[4]

This Disease Is Related to 17 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CLEC10A	OTD8HQT6	Limited	Biomarker	[5]
ISCU	OTSW6DQP	Limited	Biomarker	[5]
BPTF	OTD1RZAD	Strong	Biomarker	[6]
CBFA2T3	OTOJ10S1	Strong	Biomarker	[7]
CCDC28A	OTSWUMXT	Strong	Genetic Variation	[8]
ESPL1	OTMGEVOK	Strong	Biomarker	[9]
EVPL	OTZIAFEK	Strong	Genetic Variation	[10]
FXR2	OTQX7ATF	Strong	Altered Expression	[11]
GATA1	OTX1R7O1	Strong	Genetic Variation	[12]
GLIS2	OTOUUV1X	Strong	Biomarker	[7]
MAL	OTBM30SW	Strong	Altered Expression	[13]
MECOM	OTP983W8	Strong	Biomarker	[14]
MNX1	OTXP9FH1	Strong	Altered Expression	[15]
MRTFA	OTCVXASM	Strong	Genetic Variation	[16]
NUP98	OTNT12G2	Strong	Genetic Variation	[6]
RBM15	OT8ZPGWF	Strong	Biomarker	[17]
RBM6	OTI99KAZ	Strong	Biomarker	[18]

References

• [1] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [2] Cytarabine FDA Label
• [3] Idarubicin FDA Label
• [4] NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern.Leukemia. 2013 Dec;27(12):2280-8. doi: 10.1038/leu.2013.87. Epub 2013 Mar 27.
• [5] Induction of the erythropoietin receptor gene and acquisition of responsiveness to erythropoietin by stem cell factor in HML/SE, a human leukemic cell line.J Biol Chem. 1998 Jul 3;273(27):16921-6. doi: 10.1074/jbc.273.27.16921.
• [6] NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy.Genes Chromosomes Cancer. 2018 Jun;57(6):311-319. doi: 10.1002/gcc.22532. Epub 2018 Mar 28.
• [7] ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia.Cancer Cell. 2017 Mar 13;31(3):452-465. doi: 10.1016/j.ccell.2017.02.006.
• [8] Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98-C6orf80 fusion in a case of acute megakaryoblastic leukemia.Genes Chromosomes Cancer. 2005 Nov;44(3):225-32. doi: 10.1002/gcc.20233.
• [9] Cohesin gene mutations in tumorigenesis: from discovery to clinical significance.BMB Rep. 2014 Jun;47(6):299-310. doi: 10.5483/bmbrep.2014.47.6.092.
• [10] De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome.J Hematol Oncol. 2011 Nov 10;4:45. doi: 10.1186/1756-8722-4-45.
• [11] Cloning and characterization of the novel chimeric gene p53/FXR2 in the acute megakaryoblastic leukemia cell line CMK11-5.Tohoku J Exp Med. 2006 Jul;209(3):169-80. doi: 10.1620/tjem.209.169.
• [12] Triplications of human chromosome 21 orthologous regions in mice result in expansion of megakaryocyte-erythroid progenitors and reduction of granulocyte-macrophage progenitors.Oncotarget. 2017 Dec 19;9(4):4773-4786. doi: 10.18632/oncotarget.23463. eCollection 2018 Jan 12.
• [13] The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model.J Clin Invest. 2009 Apr;119(4):852-64. doi: 10.1172/JCI35901. Epub 2009 Mar 16.
• [14] RUNX1-EVI1 induces dysplastic hematopoiesis and acute leukemia of the megakaryocytic lineage in mice.Leuk Res. 2018 Nov;74:14-20. doi: 10.1016/j.leukres.2018.09.015. Epub 2018 Sep 26.
• [15] MNX1-ETV6 fusion gene in an acute megakaryoblastic leukemia and expression of the MNX1 gene in leukemia and normal B cell lines.Cancer Genet Cytogenet. 2008 Oct 15;186(2):115-9. doi: 10.1016/j.cancergencyto.2008.06.009.
• [16] Hemophagocytosis by leukemic megakaryoblasts in acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13;q13);RBM15-MKL1.J Pediatr Hematol Oncol. 2012 Oct;34(7):576-80. doi: 10.1097/MPH.0b013e318245a027.
• [17] New hPSC-based human models to study pediatric Acute Megakaryoblastic Leukemia harboring the fusion oncogene RBM15-MKL1.Stem Cell Res. 2017 Mar;19:1-5. doi: 10.1016/j.scr.2016.12.019. Epub 2016 Dec 19.
• [18] A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia.Blood. 2007 Jul 1;110(1):323-33. doi: 10.1182/blood-2006-10-052282. Epub 2007 Mar 14.