Details of Disease

Disease Name

Chronic myelomonocytic leukemia

chronic myelomonocytic leukaemia (CMML); CMML; chronic myelomonocytic leukemia; chronic myelomonocytic leukemia (CMML)

Definition

A myelodysplastic/myeloproliferative neoplasm which is characterized by persistent monocytosis, absence of a Philadelphia chromosome and BCR/ABL fusion gene, fewer than 20 percent blasts in the bone marrow and blood, myelodysplasia, and absence of PDGFRA or PDGFRB rearrangement.

Disease Hierarchy

DIS0C4XI: Chronic leukemia

DISDHXQ4: Myelodysplastic/myeloproliferative neoplasm

DISFCLEY: Myelodysplastic/myeloproliferative disease

DISIL8UR: Chronic myelomonocytic leukemia

Disease Identifiers

MONDO ID

MONDO_0020311

MESH ID

D015477

UMLS CUI

C0023480

MedGen ID

44125

HPO ID

HP:0012325

Orphanet ID

98823

SNOMED CT ID

127225006

General Information of Disease (ID: DISIL8UR)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Azacitidine	DMTA5OE	Approved	Small molecular drug	[1]
Sunitinib	DMCBJSR	Approved	Small molecular drug	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EZH2	TT9MZCQ	Limited	Genetic Variation	[3]
IL3RA	TTENHJ0	Disputed	Biomarker	[4]
CBL	TT7QT13	Strong	Genetic Variation	[5]
CD34	TTZAVYN	Strong	Biomarker	[6]
CSF3R	TTC70AJ	Strong	Genetic Variation	[7]
DNMT3A	TTJUALD	Strong	Genetic Variation	[8]
FLT3	TTGJCWZ	Strong	Genetic Variation	[9]
GP1BA	TTVB0Q9	Strong	Biomarker	[10]
HTR1B	TTK8CXU	Strong	Biomarker	[11]
JAK2	TTRMX3V	Strong	Genetic Variation	[12]
KIT	TTX41N9	Strong	Genetic Variation	[13]
PDGFRB	TTI7421	Strong	Biomarker	[14]
RUNX1	TTWIN3H	Strong	Genetic Variation	[15]
SF3B1	TTL2WUI	Strong	Biomarker	[16]
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⏷ Show the Full List of 14 DTT(s)

This Disease Is Related to 30 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BLVRB	OTHCFN2C	Limited	Genetic Variation	[17]
DDX41	OT6KEIHP	Limited	Genetic Variation	[18]
MOGS	OT99MBGB	Limited	Biomarker	[19]
PRR14L	OT290EDE	Limited	Biomarker	[20]
TET3	OT76U3YF	Limited	Biomarker	[21]
TRIM33	OT0KS4J7	Limited	Biomarker	[22]
CNTNAP1	OT5Y03EU	moderate	Genetic Variation	[23]
AGFG2	OTXQZHCR	Strong	Genetic Variation	[24]
ASXL1	OTX931AW	Strong	Biomarker	[25]
ELL	OTCBN5LF	Strong	Genetic Variation	[26]
ETNK1	OTDKB4DQ	Strong	Genetic Variation	[27]
ETV6	OTCZMG61	Strong	Genetic Variation	[28]
FIP1L1	OTF91GTL	Strong	Biomarker	[29]
GATA2	OTBP2QQ2	Strong	Altered Expression	[30]
GFM1	OTUN4V3N	Strong	Biomarker	[31]
HIP1	OT7AKCFQ	Strong	Biomarker	[32]
IL3	OT0CQ35N	Strong	Biomarker	[33]
KAT7	OTUN98IC	Strong	Altered Expression	[24]
KDM6A	OTZM3MJJ	Strong	Genetic Variation	[34]
NELL2	OTS4MJZ7	Strong	Biomarker	[35]
NUP98	OTNT12G2	Strong	Altered Expression	[24]
PPP1R11	OTSHYPPW	Strong	Biomarker	[6]
RABEP1	OTQROTGT	Strong	Genetic Variation	[36]
RARS1	OTHPZ6JN	Strong	Biomarker	[37]
RGPD2	OTMUZ0HX	Strong	Genetic Variation	[24]
SETBP1	OTKGCOSR	Strong	Biomarker	[38]
SMC1A	OT9ZMRK9	Strong	Genetic Variation	[28]
SRSF2	OTVDHO6U	Strong	Biomarker	[39]
TET2	OTKKT03T	Strong	Biomarker	[38]
MYH10	OTXN2WXS	Definitive	Biomarker	[40]
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⏷ Show the Full List of 30 DOT(s)

References

1	Azacitidine FDA Label
2	Sunitinib FDA Label
3	TET2 mutations are associated with specific 5-methylcytosine and 5-hydroxymethylcytosine profiles in patients with chronic myelomonocytic leukemia.PLoS One. 2012;7(2):e31605. doi: 10.1371/journal.pone.0031605. Epub 2012 Feb 6.
4	Specific skin lesions in chronic myelomonocytic leukemia: a spectrum of myelomonocytic and dendritic cell proliferations: a study of 42 cases.Am J Surg Pathol. 2012 Sep;36(9):1302-16. doi: 10.1097/PAS.0b013e31825dd4de.
5	CBL mutation and MEFV single-nucleotide variant are important genetic predictors of tumor reduction in glucocorticoid-treated patients with chronic myelomonocytic leukemia.Int J Hematol. 2018 Jul;108(1):47-57. doi: 10.1007/s12185-018-2436-0. Epub 2018 Mar 29.
6	Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies.Cancers (Basel). 2019 Oct 3;11(10):1493. doi: 10.3390/cancers11101493.
7	Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia.Oncotarget. 2017 Mar 28;8(13):20834-20841. doi: 10.18632/oncotarget.15355.
8	Overexpression of Arginase 1 is linked to DNMT3A and TET2 mutations in lower-grade myelodysplastic syndromes and chronic myelomonocytic leukemia.Leuk Res. 2018 Feb;65:5-13. doi: 10.1016/j.leukres.2017.12.003. Epub 2017 Dec 6.
9	Chronic myelomonocytic leukemia with double-mutations in DNMT3A and FLT3-ITD treated with decitabine and sorafenib.Cancer Biol Ther. 2017 Nov 2;18(11):843-849. doi: 10.1080/15384047.2017.1281491. Epub 2017 Jan 19.
10	Chronic myelomonocytic leukemia: The role of bone marrow biopsy immunohistology.Mod Pathol. 2006 Dec;19(12):1536-45. doi: 10.1038/modpathol.3800707. Epub 2006 Oct 13.
11	Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML.Sci Rep. 2018 Sep 17;8(1):13883. doi: 10.1038/s41598-018-32306-4.
12	Utility of JAK2 V617F allelic burden in distinguishing chronic myelomonocytic Leukemia from Primary myelofibrosis with monocytosis.Hum Pathol. 2019 Mar;85:290-298. doi: 10.1016/j.humpath.2018.10.026. Epub 2018 Nov 15.
13	A variant c-KIT mutation, D816H, fundamental to the sequential development of an ovarian mixed germ cell tumor and systemic mastocytosis with chronic myelomonocytic leukemia.Pediatr Blood Cancer. 2017 Apr;64(4). doi: 10.1002/pbc.26282. Epub 2016 Oct 26.
14	Molecular cytogenetic findings in a four-way t(1;12;5;12)(p36;p13;q33;q24) underlying the ETV6-PDGFRB fusion gene in chronic myelomonocytic leukemia.Cancer Genet Cytogenet. 2007 Jul 1;176(1):67-71. doi: 10.1016/j.cancergencyto.2007.03.004.
15	RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia.J Hematol Oncol. 2019 Oct 22;12(1):104. doi: 10.1186/s13045-019-0789-3.
16	Validation of the 2017 revision of the WHO chronic myelomonocytic leukemia categories.Blood Adv. 2018 Aug 14;2(15):1807-1816. doi: 10.1182/bloodadvances.2018019224.
17	Mutations within the FLR exon of NF1 are rare in myelodysplastic syndromes and acute myelocytic leukemias.Leukemia. 1993 Jul;7(7):1058-60.
18	DDX41 mutations in myeloid neoplasms are associated with male gender, TP53 mutations and high-risk disease.Am J Hematol. 2019 Jul;94(7):757-766. doi: 10.1002/ajh.25486. Epub 2019 May 7.
19	An unusual cytogenetic abnormality involving chromosomes 1 and 7 in a case of chronic myelomonocytic leukemia.Cancer Genet Cytogenet. 1995 Nov;85(1):75-7. doi: 10.1016/0165-4608(95)00139-5.
20	PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.Leukemia. 2019 May;33(5):1184-1194. doi: 10.1038/s41375-018-0340-5. Epub 2018 Dec 20.
21	Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies.Blood. 2009 Jul 2;114(1):144-7. doi: 10.1182/blood-2009-03-210039. Epub 2009 May 6.
22	Transcription intermediary factor 1 is a tumor suppressor in mouse and human chronic myelomonocytic leukemia.J Clin Invest. 2011 Jun;121(6):2361-70. doi: 10.1172/JCI45213. Epub 2011 May 2.
23	p190 bcr-abl rearrangement: a secondary cytogenetic event in some chronic myeloid disorders?.Haematologica. 1999 Dec;84(12):1075-80.
24	NUP98-HBO1-fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis.Blood Adv. 2019 Apr 9;3(7):1047-1060. doi: 10.1182/bloodadvances.2018025007.
25	Clinical, molecular, and prognostic correlates of number, type, and functional localization of TET2 mutations in chronic myelomonocytic leukemia (CMML)-a study of 1084 patients.Leukemia. 2020 May;34(5):1407-1421. doi: 10.1038/s41375-019-0690-7. Epub 2019 Dec 13.
26	A novel variant form of MLL-ELL fusion transcript with t(11;19)(q23;p13.1) in chronic myelomonocytic leukemia transforming to acute myeloid leukemia.Cancer Genet Cytogenet. 2008 Jul 15;184(2):109-12. doi: 10.1016/j.cancergencyto.2008.04.001.
27	Novel recurrent mutations in ethanolamine kinase 1 (ETNK1) gene in systemic mastocytosis with eosinophilia and chronic myelomonocytic leukemia.Blood Cancer J. 2015 Jan 23;5(1):e275. doi: 10.1038/bcj.2014.94.
28	Chronic myelomonocytic leukemia with ETV6-ABL1 rearrangement and SMC1A mutation.Cancer Genet. 2019 Oct;238:31-36. doi: 10.1016/j.cancergen.2019.07.004. Epub 2019 Jul 13.
29	Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute myeloid leukemia transformation of chronic myelomonocytic leukemia.J Hematol Oncol. 2014 Mar 27;7:26. doi: 10.1186/1756-8722-7-26.
30	GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice.Cancer Sci. 2019 Apr;110(4):1183-1193. doi: 10.1111/cas.13959. Epub 2019 Feb 23.
31	Prognostic Role of Gene Mutations in Chronic Myelomonocytic Leukemia Patients Treated With Hypomethylating Agents.EBioMedicine. 2018 May;31:174-181. doi: 10.1016/j.ebiom.2018.04.018. Epub 2018 Apr 25.
32	Sensitivity to imatinib but low frequency of the TEL/PDGFRbeta fusion protein in chronic myelomonocytic leukemia.Haematologica. 2003 Apr;88(4):408-15.
33	Engraftment of chronic myelomonocytic leukemia cells in immunocompromised mice supports disease dependency on cytokines.Blood Adv. 2017 Jun 13;1(14):972-979. doi: 10.1182/bloodadvances.2017004903. eCollection 2017 Jun 13.
34	Utx loss causes myeloid transformation.Leukemia. 2018 Jun;32(6):1458-1465. doi: 10.1038/s41375-018-0011-6. Epub 2018 Feb 2.
35	Myeloid leukemias express a broad spectrum of VEGF receptors including neuropilin-1 (NRP-1) and NRP-2.Leuk Lymphoma. 2007 Oct;48(10):1997-2007. doi: 10.1080/10428190701534424.
36	Activity of STI571 in chronic myelomonocytic leukemia with a platelet-derived growth factor beta receptor fusion oncogene.Blood. 2002 Aug 1;100(3):1088-91. doi: 10.1182/blood-2002-01-0165.
37	The incidence of myelodysplastic syndromes in Western Greece is increasing.Ann Hematol. 2013 Jul;92(7):877-87. doi: 10.1007/s00277-013-1712-6. Epub 2013 Apr 10.
38	Comprehensive mutation profiling and mRNA expression analysis in atypical chronic myeloid leukemia in comparison with chronic myelomonocytic leukemia.Cancer Med. 2019 Feb;8(2):742-750. doi: 10.1002/cam4.1946. Epub 2019 Jan 11.
39	Prognostic significance of SRSF2 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: a meta-analysis.Hematology. 2018 Dec;23(10):778-784. doi: 10.1080/10245332.2018.1471794. Epub 2018 May 14.
40	MYH10 protein expression in platelets as a biomarker of RUNX1 and FLI1 alterations.Blood. 2012 Sep 27;120(13):2719-22. doi: 10.1182/blood-2012-04-422352. Epub 2012 Jun 7.