Details of Disease

General Information of Disease (ID: DISNQ2OY)

• Disease Name: Systemic mastocytosis
• Synonyms: SM; systemic mast cell disease; systemic mastocytosis with associated hemotologic non-mast cell lineage disease (SM-AHNMD); Agressive systemic mastocytosis; Mast cell disease; SMCD - systemic mast cell disease; systemic tissue Mast cell disease; systemic tissue mast cell disease; systemic mastocytosis
• Disease Class: 2A21: Mastocytosis
• Definition: Systemic mastocytosis (SM) comprises a heterogeneous group of rare acquired and chronic hematological malignancies that are related to an abnormal proliferation of mast cells in tissue, including bone marrow, with or without skin involvement.
• Disease Hierarchy:
  DIS1TEE0: Mastocytosis
  DISNQ2OY: Systemic mastocytosis
• ICD Code:
  ICD-11: ICD-11: 2A21.0
  ICD-9: ICD-9: 202.6, 757.33
  Expand ICD-11: '2A21.0
  Expand ICD-9: 202.6,757.33
• Disease Identifiers:
  MONDO ID: MONDO_0016586
  MESH ID: D034721
  UMLS CUI: C0221013
  MedGen ID: 67436
  Orphanet ID: 2467
  SNOMED CT ID: 1255137009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Avapritinib	DMK2GZX	Approved	NA	[1]
Imatinib	DM7RJXL	Approved	Small molecular drug	[2]
Midostaurin	DMI6E0R	Approved	Small molecular drug	[3]
Ripretinib	DM958QB	Approved	NA	[4]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
PA101B	DMAMOQ9	Phase 2	NA	[1]
GTB-3550	DMK2RIB	Phase 1/2	Recombinant protein	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CBL	TT7QT13	moderate	Genetic Variation	[6]
CDA	TTQ12RK	moderate	Biomarker	[7]
ENPP3	TTD4TKP	moderate	Biomarker	[8]
FLT3	TTGJCWZ	moderate	Genetic Variation	[9]
IL2RA	TT10Y9E	moderate	Altered Expression	[10]
PRKG2	TTDWFCQ	moderate	Biomarker	[11]
SIRPA	TTBRJS9	moderate	Altered Expression	[12]
CD2	TTJDUNO	Strong	Altered Expression	[13]
CD52	TTQT5S9	Strong	Biomarker	[14]
FCER2	TTCH6MU	Strong	Biomarker	[15]
HDC	TTV9GOF	Strong	Biomarker	[16]
HMOX1	TTI6V2A	Strong	Biomarker	[17]
SMPD1	TTJTM88	Strong	Biomarker	[6]
PDGFRA	TT8FYO9	Definitive	Genetic Variation	[18]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ISM1	OTZTK2TV	Limited	Biomarker	[19]
STAT5A	OTBSJGN3	Limited	Biomarker	[20]
STAT5B	OTZVPEBT	Limited	Biomarker	[20]
CASK	OT8EF7ZF	moderate	Biomarker	[21]
CBFB	OTIAC6W4	moderate	Genetic Variation	[22]
CHIC2	OTNE3T6Z	moderate	Genetic Variation	[23]
FIP1L1	OTF91GTL	moderate	Biomarker	[24]
ISG20	OTCWRJJW	moderate	Altered Expression	[10]
SRSF2	OTVDHO6U	moderate	Genetic Variation	[25]
ASXL1	OTX931AW	Strong	Genetic Variation	[25]
CLEC11A	OT9KBH7C	Strong	Genetic Variation	[26]
CLEC4D	OTT7X1UC	Strong	Genetic Variation	[27]
ETNK1	OTDKB4DQ	Strong	Genetic Variation	[28]
FH	OTEQWU6Q	Strong	Genetic Variation	[27]
NELL2	OTS4MJZ7	Strong	Biomarker	[29]
RUNX1T1	OT30DED5	Strong	Genetic Variation	[22]
TET2	OTKKT03T	Strong	Genetic Variation	[6]
TNFSF8	OTDYGDJ3	Strong	Biomarker	[30]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
• [3] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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.
• [6] Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival.Am J Hematol. 2016 Sep;91(9):888-93. doi: 10.1002/ajh.24426. Epub 2016 Jun 20.
• [7] Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia.Oncotarget. 2017 Aug 7;8(47):82897-82909. doi: 10.18632/oncotarget.19970. eCollection 2017 Oct 10.
• [8] In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis.Blood Adv. 2019 Feb 26;3(4):633-643. doi: 10.1182/bloodadvances.2018026179.
• [9] Midostaurin for the management of FLT3-mutated acute myeloid leukemia and advanced systemic mastocytosis.Am J Health Syst Pharm. 2019 Feb 9;76(5):268-274. doi: 10.1093/ajhp/zxy050.
• [10] Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis.Int J Mol Sci. 2019 Jan 28;20(3):552. doi: 10.3390/ijms20030552.
• [11] Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion.Haematologica. 2008 Jan;93(1):49-56. doi: 10.3324/haematol.11836.
• [12] Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRPalpha), CD47, and SHP-1.J Leukoc Biol. 2005 Jun;77(6):984-92. doi: 10.1189/jlb.0604349. Epub 2005 Mar 22.
• [13] 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.
• [14] CD52 is a molecular target in advanced systemic mastocytosis.FASEB J. 2014 Aug;28(8):3540-51. doi: 10.1096/fj.14-250894. Epub 2014 Apr 23.
• [15] An unusual case of systemic mastocytosis associated with chronic lymphocytic leukaemia (SM-CLL).J Clin Pathol. 2006 Mar;59(3):264-8. doi: 10.1136/jcp.2005.026989.
• [16] Immunohistochemical detection of histidine decarboxylase in neoplastic mast cells in patients with systemic mastocytosis.Hum Pathol. 2006 Apr;37(4):439-47. doi: 10.1016/j.humpath.2005.11.015. Epub 2006 Feb 7.
• [17] Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells.Blood. 2007 Jul 15;110(2):661-9. doi: 10.1182/blood-2006-10-054411. Epub 2007 Apr 9.
• [18] The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis.Haematologica. 2018 May;103(5):799-809. doi: 10.3324/haematol.2017.179895. Epub 2018 Feb 8.
• [19] 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.
• [20] CD44 is a RAS/STAT5-regulated invasion receptor that triggers disease expansion in advanced mastocytosis.Blood. 2018 Nov 1;132(18):1936-1950. doi: 10.1182/blood-2018-02-833582. Epub 2018 Jul 17.
• [21] Investigation of mast cell toll-like receptor 3 in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Systemic Mastocytosis using the novel application of autoMACS magnetic separation and flow cytometry.Asian Pac J Allergy Immunol. 2018 Dec;36(4):257-264. doi: 10.12932/AP-200517-0086.
• [22] Systemic mastocytosis is uncommon in KIT D816V mutation positive core-binding factor acute myeloid leukemia.Leuk Lymphoma. 2012 Jul;53(7):1338-44. doi: 10.3109/10428194.2011.647314. Epub 2012 Jan 31.
• [23] CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.Blood. 2003 Nov 1;102(9):3093-6. doi: 10.1182/blood-2003-05-1627. Epub 2003 Jul 3.
• [24] Mast cells and eosinophils in mastocytosis, chronic eosinophilic leukemia, and non-clonal disorders.Semin Hematol. 2012 Apr;49(2):128-37. doi: 10.1053/j.seminhematol.2012.01.007.
• [25] Incidence and prognostic impact of cytogenetic aberrations in patients with systemic mastocytosis.Genes Chromosomes Cancer. 2018 May;57(5):252-259. doi: 10.1002/gcc.22526. Epub 2018 Feb 19.
• [26] Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes.J Allergy Clin Immunol. 2010 Mar;125(3):719-26, 726.e1-726.e4. doi: 10.1016/j.jaci.2009.10.020. Epub 2010 Jan 12.
• [27] The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis.Ann Hematol. 2014 Jan;93(1):81-8. doi: 10.1007/s00277-013-1964-1. Epub 2013 Nov 27.
• [28] 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.
• [29] 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.
• [30] CD30 in systemic mastocytosis.Immunol Allergy Clin North Am. 2014 May;34(2):341-55. doi: 10.1016/j.iac.2014.01.006. Epub 2014 Mar 13.