Details of Disease

General Information of Disease (ID: DIS7VQW9)

Disease Name	Mast cell leukaemia
Synonyms	SMMCL; Mast cell leukaemia; Mast cell leukemia; mast-cell leukaemia; mast-cell leukemia; aleukemic mast cell leukemia; aleukemic mast cell leukaemia
Disease Class	2A21: Mastocytosis
Definition	Mast cell leukemia is a malignant form of systemic mastocytosis (SM) characterized, most of the time, by the presence of circulating mast cells.
Disease Hierarchy	DISNAKFL: Leukemia DISNQ2OY: Systemic mastocytosis DIS7VQW9: Mast cell leukaemia
ICD Code	ICD-11 ICD-11: 2A21.00 ICD-10 ICD-10: C94.3 Expand ICD-11 '2A21.00 Expand ICD-10 'C94.3
Disease Identifiers	MONDO ID MONDO_0020334 MESH ID D007946 UMLS CUI C0023461 MedGen ID 44123 Orphanet ID 98851 SNOMED CT ID 110002002

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
Avapritinib	DMK2GZX	Approved	NA	[1]
Sunitinib	DMCBJSR	Approved	Small molecular drug	[2]
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This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
GTB-3550	DMK2RIB	Phase 1/2	Recombinant protein	[3]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SMPD1	TTJTM88	Limited	Biomarker	[4]
BTK	TTGM6VW	Strong	Altered Expression	[5]
CD2	TTJDUNO	Strong	Altered Expression	[6]
ENPP3	TTD4TKP	Strong	Altered Expression	[7]
KIT	TTX41N9	Strong	Genetic Variation	[8]
PRKG2	TTDWFCQ	Strong	Genetic Variation	[9]
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⏷ Show the Full List of 6 DTT(s)

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ISM1	OTZTK2TV	Limited	Biomarker	[10]
SOX11	OT4LG7LA	Limited	Altered Expression	[11]
LAD1	OT6YGTVX	Strong	Biomarker	[12]
NELL2	OTS4MJZ7	Strong	Biomarker	[13]
RASGRP4	OT15PWN4	Strong	Genetic Variation	[14]
SIGLEC8	OTQ5TRRV	Strong	Biomarker	[15]
SPIB	OTO4YKYI	Strong	Altered Expression	[16]
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⏷ Show the Full List of 7 DOT(s)

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	Sunitinib FDA Label
3	ClinicalTrials.gov (NCT03214666) GTB-3550 (CD16/IL-15/CD33) Tri-Specific Killer Engager (TriKE) for High Risk Heme Malignancies. U.S. National Institutes of Health.
4	Targeted Treatment Options in Mastocytosis.Front Med (Lausanne). 2017 Jul 20;4:110. doi: 10.3389/fmed.2017.00110. eCollection 2017.
5	Discovery of pyrazolopyrimidine derivatives as potent BTK inhibitors with effective anticancer activity in MCL.Bioorg Chem. 2019 Aug;89:102943. doi: 10.1016/j.bioorg.2019.102943. Epub 2019 Apr 25.
6	Recent advances in mastocytosis research. Summary of the Vienna Mastocytosis Meeting 1998.Int Arch Allergy Immunol. 1999 Sep;120(1):1-7. doi: 10.1159/000024214.
7	CD203c is overexpressed on neoplastic mast cells in systemic mastocytosis and is upregulated upon IgE receptor cross-linking.Int J Immunopathol Pharmacol. 2008 Oct-Dec;21(4):797-806. doi: 10.1177/039463200802100404.
8	Identification of a leukemia-initiating stem cell in human mast cell leukemia.Leukemia. 2019 Nov;33(11):2673-2684. doi: 10.1038/s41375-019-0460-6. Epub 2019 Apr 5.
9	Acute mast cell leukemia associated with t(4;5)(q21;q33).Hum Pathol. 2017 Sep;67:198-204. doi: 10.1016/j.humpath.2017.03.014. Epub 2017 Apr 13.
10	Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management.Am J Hematol. 2019 Mar;94(3):363-377. doi: 10.1002/ajh.25371. Epub 2019 Jan 2.
11	SOX11 expression as a MRD molecular marker for MCL in comparison with t(11;14) and IGH rearrangement.Med Oncol. 2018 Mar 8;35(4):49. doi: 10.1007/s12032-018-1111-x.
12	Preclinical human models and emerging therapeutics for advanced systemic mastocytosis.Haematologica. 2018 Nov;103(11):1760-1771. doi: 10.3324/haematol.2018.195867. Epub 2018 Jul 5.
13	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.
14	RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function.J Biol Chem. 2002 Jul 12;277(28):25756-74. doi: 10.1074/jbc.M202575200. Epub 2002 Apr 15.
15	Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells.J Allergy Clin Immunol. 2018 May;141(5):1774-1785.e7. doi: 10.1016/j.jaci.2017.06.028. Epub 2017 Jul 20.
16	Bortezomib prevents cytarabine resistance in MCL, which is characterized by down-regulation of dCK and up-regulation of SPIB resulting in high NF-B activity.BMC Cancer. 2018 Apr 25;18(1):466. doi: 10.1186/s12885-018-4346-1.