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KIT
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Interpretation 22
Tier 1
KIT
Variants
KIT D816V
KIT exon(s) 11 any
KIT exon(s) 17 any
KIT exon(s) 8 missense
KIT exon(s) 9 missense
KIT exon(s) 10 missense
KIT any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Mast Cell Neoplasm
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic Syndrome
Myelodysplastic/Myeloproliferative Neoplasm
Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
Primary Myelofibrosis
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

KIT(cKIT) mutations are present in approximately 8-25% of cases of acute myeloid leukemia and have a higher prevalence in the favorable cytogenetic risk group including core binding factor (CBF) AMLs (ie, (t(8;21)(q22;q22)(RUNX1-RUNX1T1), inv(16)(p13q22)(CBFB-MYH11)) or normal karyotype AML. Mutations of KIT in AML are most common in KIT exon 17 (within the activation loop of the tyrosine kinase domain) but may also occur in KIT exons 8 (extracellular portion of the receptor implicated in dimerization), 9-11 (juxtamembrane/transmembrane domains). The presence of KIT mutations has been reported to be associated with a poorer survival and/or higher risk of relapse than expected for patients with the t(8;21)(q22;q22)(RUNX1-RUNX1T1), and to a lesser extent, in inv(16) AML. KIT mutations are also important in systemic mastocytosis and various mast cell disorders; over 90% of cases of systemic mastocytosis carry mutations in exon 17 of KIT (most commonly D816V or rarely D816H, D816Y or other variants). In patients with mastocytosis, the KIT mutations may be detectable in non-mast cell hematopoietic cells. The KIT D816V mutation has been shown to be resistant to imatinib; other KIT mutations may show variable responses to imatinib. The KIT D816V mutant has been reported to be sensitive to other tyrosine kinase inhibitors. In the context of core binding factor AMLs, the KIT mutation status can help direct therapeutic management.

Citations
  1. Kihara R, et al. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 2014;28(8):1586-95
  2. Erben P, et al. The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis. Ann Hematol 2014;93(1):81-8
  3. Kristensen T, et al. Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis. Am J Hematol 2014;89(5):493-8
  4. Agarwal R, et al. KIT D816V mutation detection: a comparative study using peripheral blood, bone marrow aspirate and bone marrow trephine samples for detection of KIT mutations in patients with systemic mastocytosis. Leuk Lymphoma 2014;55(9):2202-3
  5. Furitsu T, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest 1993;92(4):1736-44
  6. Kanakura Y, et al. Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia cell line. Leukemia 1994;8 Suppl 1():S18-22
  7. Nagata H, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci U S A 1995;92(23):10560-4
  8. Beghini A, et al. In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation. Blood Cells Mol Dis 1998;24(2):262-70
  9. Pullarkat VA, et al. Mast cell disease associated with acute myeloid leukemia: detection of a new c-kit mutation Asp816His. Am J Hematol 2000;65(4):307-9
  10. Frost MJ, et al. Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant. Mol Cancer Ther 2002;1(12):1115-24
  11. Zermati Y, et al. Effect of tyrosine kinase inhibitor STI571 on the kinase activity of wild-type and various mutated c-kit receptors found in mast cell neoplasms. Oncogene 2003;22(5):660-4
  12. Pullarkat VA, et al. Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: analysis of clinicopathologic features and activating c-kit mutations. Am J Hematol 2003;73(1):12-7
  13. Akin C, et al. A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood 2004;103(8):3222-5
  14. Zhang LY, et al. A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy. Leuk Res 2006;30(4):373-8
  15. Garcia-Montero AC, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood 2006;108(7):2366-72
  16. Corless CL, et al. Allele-specific polymerase chain reaction for the imatinib-resistant KIT D816V and D816F mutations in mastocytosis and acute myelogenous leukemia. J Mol Diagn 2006;8(5):604-12
  17. Manara E, et al. Core-binding factor acute myeloid leukemia in pediatric patients enrolled in the AIEOP AML 2002/01 trial: screening and prognostic impact of c-KIT mutations. Leukemia 2014;28(5):1132-4
  18. Su L, et al. NPM1, FLT3-ITD, CEBPA, and c-kit mutations in 312 Chinese patients with de novo acute myeloid leukemia. Hematology 2014;19(6):324-8
  19. Kim HJ, et al. KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement. Ann Hematol 2013;92(2):163-71
  20. Verstovsek S Advanced systemic mastocytosis: the impact of KIT mutations in diagnosis, treatment, and progression. Eur J Haematol 2013;90(2):89-98
  21. Malaise M, et al. Clinical implications of c-Kit mutations in acute myelogenous leukemia. Curr Hematol Malig Rep 2009;4(2):77-82
  22. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia (Version 1.2018).
Last updated: 2018-11-12 20:41:34 UTC
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