Details of Disease

Disease Name

Acute megakaryoblastic leukemia

megakaryocytic leukaemia; acute myeloblastic leukemia type 7; megakaryocytic leukemia; acute myeloblastic leukaemia type 7; AML M7; acute myeloid leukaemia M7; acute megakaryoblastic leukemia; acute megakaryocytic leukaemia; acute megakaryoblastic leukaemia (FAB type M7); acute megakaryocytic leukemias; thrombocytic leukaemia; acute M7 myeloid leukaemia; thrombocytic leukemia; leukemia, megakaryocytic, malignant; acute megakaryocytic leukemia; AMKL; acute myeloid leukemia M7; megakaryocytic myelosis; FAB M7; acute megakaryoblastic leukemia (FAB type M7); acute megakaryoblastic leukemia, FAB M7; acute M7 myeloid leukemia

Definition

Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) that occurs predominantly in childhood and particularly in children with Down syndrome (DS-AMKL). Nonspecific symptoms may be irritability, weakness, and dizziness while specific symptoms include pallor, fever, mucocutaneous bleeding, hepatosplenomegaly, neurological manifestations and rarely lymphadenopathy. Acute panmyelosis with myelofibrosis may also be associated with AMKL. In contrast to DS-AMKL (around 80 % survival), non-DS-AMKL is an AML subgroup associated with poor prognosis.

Disease Hierarchy

DIS0BM1I: Acute myeloid leukaemia

DIS0JX3M: Acute megakaryoblastic leukemia

Disease Identifiers

MONDO ID

MONDO_0018872

MESH ID

D007947

UMLS CUI

C0023462

MedGen ID

44124

HPO ID

HP:0006733

Orphanet ID

518

SNOMED CT ID

188754005

General Information of Disease (ID: DIS0JX3M)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
JAK3	TTT7PJU	Limited	Genetic Variation	[1]
ANK1	TTKFPMH	Strong	Altered Expression	[2]
APCS	TTB7VAT	Strong	Biomarker	[3]
BIRC5	TTTPU1G	Strong	Therapeutic	[4]
CBS	TTVZJ7G	Strong	Altered Expression	[5]
CDA	TTQ12RK	Strong	Genetic Variation	[6]
CXCL9	TTWE5PB	Strong	Biomarker	[7]
DYRK1A	TTSBVFO	Strong	Biomarker	[8]
GP1BA	TTVB0Q9	Strong	Genetic Variation	[9]
PF4	TTSG7Q5	Strong	Altered Expression	[10]
RUNX1	TTWIN3H	Strong	Genetic Variation	[11]
SLC25A1	TTTD730	Strong	Biomarker	[12]
THPO	TTCG5PE	Strong	Biomarker	[13]
TIRAP	TTKU0LS	Strong	Genetic Variation	[14]
PTGIR	TTOFYT1	Definitive	Biomarker	[15]
------------------------------------------------------------------------------------


⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CMPK1	DEMPH4I	Strong	Biomarker	[7]
------------------------------------------------------------------------------------

This Disease Is Related to 48 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
A4GALT	OTPX3UGY	Strong	Biomarker	[16]
AP3B1	OTYTIH5Q	Strong	Altered Expression	[17]
APOC1	OTA58CED	Strong	Biomarker	[18]
APOC2	OTLINYIQ	Strong	Biomarker	[19]
BPTF	OTD1RZAD	Strong	Biomarker	[20]
CCDC28A	OTSWUMXT	Strong	Genetic Variation	[21]
CD8A	OTDWQJXK	Strong	Genetic Variation	[14]
ERG	OTOTX9VU	Strong	Biomarker	[22]
ESPL1	OTMGEVOK	Strong	Biomarker	[23]
EVPL	OTZIAFEK	Strong	Genetic Variation	[24]
FXR2	OTQX7ATF	Strong	Altered Expression	[25]
GFI1B	OTRDW8YO	Strong	Altered Expression	[7]
GLIS1	OTBDNB26	Strong	Genetic Variation	[26]
GLIS3	OTBC960E	Strong	Genetic Variation	[26]
GNLY	OTZJKA8C	Strong	Altered Expression	[27]
HOXC5	OTPQTLKZ	Strong	Altered Expression	[28]
IL3	OT0CQ35N	Strong	Biomarker	[29]
ITGA2B	OT4Y17PY	Strong	Biomarker	[30]
MECOM	OTP983W8	Strong	Biomarker	[11]
MLLT10	OTURMDV7	Strong	Genetic Variation	[31]
MLLT3	OTXH4DDG	Strong	Genetic Variation	[14]
MNX1	OTXP9FH1	Strong	Altered Expression	[32]
MRTFA	OTCVXASM	Strong	Genetic Variation	[33]
MRTFB	OT9OXGS9	Strong	Biomarker	[34]
MYH11	OTVNVWY3	Strong	Biomarker	[35]
MYOCD	OTSJNHTH	Strong	Biomarker	[36]
NUP98	OTNT12G2	Strong	Biomarker	[37]
PFN2	OT5SSSA7	Strong	Biomarker	[38]
PICALM	OTQVRPMQ	Strong	Biomarker	[39]
PRB1	OTV0SYMD	Strong	Biomarker	[40]
PTPN4	OT6SXU5Y	Strong	Biomarker	[41]
RBM15	OT8ZPGWF	Strong	Genetic Variation	[20]
RBM6	OTI99KAZ	Strong	Biomarker	[29]
SCIN	OT6U09OL	Strong	Altered Expression	[42]
SH2D1A	OTLU49I5	Strong	Biomarker	[3]
SNAP91	OTE3EXWZ	Strong	Altered Expression	[43]
SPEN	OT37A2MD	Strong	Genetic Variation	[44]
SRF	OTW18FQN	Strong	Biomarker	[45]
SUMO3	OTTUJQJ1	Strong	Biomarker	[46]
TMEM241	OTYO8A3P	Strong	Biomarker	[19]
TNS1	OTZ8S1PL	Strong	Altered Expression	[47]
TRIB1	OTPEO17G	Strong	Genetic Variation	[48]
CBFA2T3	OTOJ10S1	Definitive	Genetic Variation	[49]
FANCB	OTMZTXB5	Definitive	Genetic Variation	[50]
GLIS2	OTOUUV1X	Definitive	Biomarker	[49]
HBG1	OTVL4NSU	Definitive	Altered Expression	[51]
HBG2	OT4J48JJ	Definitive	Altered Expression	[51]
MAL	OTBM30SW	Definitive	Genetic Variation	[14]
------------------------------------------------------------------------------------


⏷ Show the Full List of 48 DOT(s)

References

1	Description of a novel Janus kinase 3 P132A mutation in acute megakaryoblastic leukemia and demonstration of previously reported Janus kinase 3 mutations in normal subjects.Leuk Lymphoma. 2011 Sep;52(9):1742-50. doi: 10.3109/10428194.2011.574757. Epub 2011 May 23.
2	MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of Down syndrome.Blood. 2015 Feb 19;125(8):1292-301. doi: 10.1182/blood-2014-06-581892. Epub 2014 Dec 22.
3	Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling.Mol Oncol. 2015 Oct;9(8):1510-27. doi: 10.1016/j.molonc.2015.04.003. Epub 2015 Apr 30.
4	Disruption of the inhibitor of apoptosis protein survivin sensitizes Bcr-abl-positive cells to STI571-induced apoptosis. Cancer Res. 2005 Sep 15;65(18):8224-32. doi: 10.1158/0008-5472.CAN-05-0303.
5	Down syndrome, drug metabolism and chromosome 21.Pediatr Blood Cancer. 2005 Jan;44(1):33-9. doi: 10.1002/pbc.20092.
6	The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines. Cancer Res. 2004 Jan 15;64(2):728-35.
7	Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate.Br J Haematol. 2007 Jan;136(2):212-9. doi: 10.1111/j.1365-2141.2006.06407.x. Epub 2006 Dec 8.
8	Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megakaryoblastic leukemia in a murine model of Down syndrome.J Clin Invest. 2012 Mar;122(3):948-62. doi: 10.1172/JCI60455. Epub 2012 Feb 22.
9	Acute panmyelosis with myelofibrosis: an entity distinct from acute megakaryoblastic leukemia.Mod Pathol. 2005 May;18(5):603-14. doi: 10.1038/modpathol.3800348.
10	Platelet factor 4 mRNA expression in cells from a patient with megakaryoblastic crisis of chronic myelogenous leukemia.Cancer. 1991 Feb 15;67(4):960-4. doi: 10.1002/1097-0142(19910215)67:4<960::aid-cncr2820670418>3.0.co;2-v.
11	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.
12	GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia.J Natl Cancer Inst. 2005 Feb 2;97(3):226-31. doi: 10.1093/jnci/dji026.
13	Molecular cloning and functional expression of feline thrombopoietin.Vet Immunol Immunopathol. 1998 Dec 11;66(3-4):225-36. doi: 10.1016/s0165-2427(98)00190-1.
14	Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study.Blood. 2015 Sep 24;126(13):1575-84. doi: 10.1182/blood-2015-02-629204. Epub 2015 Jul 27.
15	Cloning and expression of a cDNA for the human prostacyclin receptor.FEBS Lett. 1994 May 9;344(1):74-8. doi: 10.1016/0014-5793(94)00355-6.
16	Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells: implication in the sensitivity to verotoxins.J Biol Chem. 2002 Mar 29;277(13):11247-54. doi: 10.1074/jbc.M109519200. Epub 2002 Jan 8.
17	Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.Thromb Haemost. 2017 Jan 5;117(1):105-115. doi: 10.1160/TH16-01-0045. Epub 2016 Oct 20.
18	Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome.Leukemia. 2004 Oct;18(10):1617-23. doi: 10.1038/sj.leu.2403466.
19	Integrated differential transcriptome maps of Acute Megakaryoblastic Leukemia (AMKL) in children with or without Down Syndrome (DS).BMC Med Genomics. 2014 Dec 5;7:63. doi: 10.1186/s12920-014-0063-z.
20	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.
21	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.
22	Early lineage priming by trisomy of Erg leads to myeloproliferation in a Down syndrome model.PLoS Genet. 2015 May 14;11(5):e1005211. doi: 10.1371/journal.pgen.1005211. eCollection 2015 May.
23	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.
24	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.
25	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.
26	Emerging Roles of GLI-Similar Krppel-like Zinc Finger Transcription Factors in Leukemia and Other Cancers.Trends Cancer. 2019 Sep;5(9):547-557. doi: 10.1016/j.trecan.2019.07.005. Epub 2019 Aug 20.
27	Expression of granulysin mRNA in the human megakaryoblastic leukemia cell line CMK.Acta Haematol. 2002;108(1):13-8. doi: 10.1159/000063061.
28	Differentiation and cell-type-restricted expression of HOXC4, HOXC5 and HOXC6 in myeloid leukemias and normal myeloid cells.Leukemia. 1998 Nov;12(11):1724-32. doi: 10.1038/sj.leu.2401106.
29	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.
30	Effect of recombinant human interferons in inducing differentiation of acute megakaryoblastic leukaemia blast cells.Leuk Lymphoma. 1995 Jan;16(3-4):329-33. doi: 10.3109/10428199509049772.
31	MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.Leuk Res. 2005 Oct;29(10):1223-6. doi: 10.1016/j.leukres.2005.03.008. Epub 2005 Apr 11.
32	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.
33	MKL1 mediates TGF--induced CTGF transcription to promote renal fibrosis.J Cell Physiol. 2020 May;235(5):4790-4803. doi: 10.1002/jcp.29356. Epub 2019 Oct 21.
34	Divergent Regulation of Actin Dynamics and Megakaryoblastic Leukemia-1 and -2 (Mkl1/2) by cAMP in Endothelial and Smooth Muscle Cells.Sci Rep. 2017 Jun 16;7(1):3681. doi: 10.1038/s41598-017-03337-0.
35	Gene expression profiling of pediatric acute myelogenous leukemia.Blood. 2004 Dec 1;104(12):3679-87. doi: 10.1182/blood-2004-03-1154. Epub 2004 Jun 29.
36	MiR-93-5p inhibits the EMT of breast cancer cells via targeting MKL-1 and STAT3.Exp Cell Res. 2017 Aug 1;357(1):135-144. doi: 10.1016/j.yexcr.2017.05.007. Epub 2017 May 9.
37	Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities.Blood Adv. 2019 Nov 12;3(21):3307-3321. doi: 10.1182/bloodadvances.2019030981.
38	The myocardin-related transcription factor MKL co-regulates the cellular levels of two profilin isoforms.J Biol Chem. 2017 Jul 14;292(28):11777-11791. doi: 10.1074/jbc.M117.781104. Epub 2017 May 25.
39	High incidence of CALM-AF10 fusion and the identification of a novel fusion transcript in acute megakaryoblastic leukemia in children without Down's syndrome.Leukemia. 2007 Feb;21(2):352-3. doi: 10.1038/sj.leu.2404503. Epub 2006 Dec 14.
40	Molecular pathways: induction of polyploidy as a novel differentiation therapy for leukemia.Clin Cancer Res. 2013 Nov 15;19(22):6084-8. doi: 10.1158/1078-0432.CCR-12-2604. Epub 2013 Aug 20.
41	Arsenic trioxide mediates intrinsic and extrinsic pathways of apoptosis and cell cycle arrest in acute megakaryocytic leukemia. Int J Oncol. 2005 Aug;27(2):537-45.
42	Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis.Blood. 2001 Oct 1;98(7):2210-9. doi: 10.1182/blood.v98.7.2210.
43	Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia.Leukemia. 2001 Jun;15(6):910-4. doi: 10.1038/sj.leu.2402140.
44	Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia.Proc Natl Acad Sci U S A. 2001 May 8;98(10):5776-9. doi: 10.1073/pnas.101001498.
45	Involvement of SRF coactivator MKL2 in BDNF-mediated activation of the synaptic activity-responsive element in the Arc gene.J Neurochem. 2019 Jan;148(2):204-218. doi: 10.1111/jnc.14596. Epub 2018 Nov 12.
46	A 15q24 microdeletion in transient myeloproliferative disease (TMD) and acute megakaryoblastic leukaemia (AMKL) implicates PML and SUMO3 in the leukaemogenesis of TMD/AMKL.Br J Haematol. 2012 Apr;157(2):180-7. doi: 10.1111/j.1365-2141.2012.09028.x. Epub 2012 Feb 1.
47	Tensin 1 Is Essential for Myofibroblast Differentiation and Extracellular Matrix Formation.Am J Respir Cell Mol Biol. 2017 Apr;56(4):465-476. doi: 10.1165/rcmb.2016-0104OC.
48	The role of Trib1 in myeloid leukaemogenesis and differentiation.Biochem Soc Trans. 2015 Oct;43(5):1104-7. doi: 10.1042/BST20150110.
49	Comprehensive Transcriptome Profiling of Cryptic CBFA2T3-GLIS2 Fusion-Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study.Clin Cancer Res. 2020 Feb 1;26(3):726-737. doi: 10.1158/1078-0432.CCR-19-1800. Epub 2019 Nov 12.
50	Acute promyelocytic leukemia and constitutional trisomy 21.Cancer Genet Cytogenet. 2006 Mar;165(2):176-9. doi: 10.1016/j.cancergencyto.2005.08.014.
51	Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome.Br J Haematol. 1995 Jul;90(3):607-14. doi: 10.1111/j.1365-2141.1995.tb05591.x.