The c-kit gene is a proto-oncogene, and its product, c-kit protein, is a tyrosine kinase. c-kit protein is an important member of tyrosine kinases and is involved in the regulation of hematopoietic stem cell proliferation and differentiation through a series of signaling pathways.
Recent studies have shown that c-kit gene mutations, especially overexpression, are strongly associated with pathogenesis, treatment, and prognosis in acute leukemia. c-kit genes are normally expressed in hematopoietic stem/progenitor cells, rarely or not in acute lymphoblastic leukemia (ALL), and rarely or not in acute myeloblastic leukemia (AML). （The expression is high in acute myeloblastic leukemia (AML), but is not uniform across subtypes of AML.
c-kit expression is higher in patients with primary AML than in AML transformed by myelodysplastic syndromes, so c-kit testing can be useful in the differential diagnosis of two different AMLs. Moreover, patients with AML with high c-kit expression have a poor prognosis and a high relapse rate, so c-kit inhibitors can be used in the treatment of hematologic neoplasms.
The current applications of c-kit inhibitors in hematologic tumors are as follows:
- Imatinib (Imatinib): is a selective BCR-ABL/PDGFR/KIT inhibitor that is currently available for the treatment of chronic myelogenous leukemia (CML) in addition to shown that imatinib in AML-M2 leukemia patients resulted in the suppression of c-kit high expressing leukemia cells by inhibiting c-kit, while also significantly enhancing the drug activity of agranulocytosis.
- Flumatinib (Fluatinib): A derivative of imatinib, it is a selective BCR-ABL/PDGFR/KIT inhibitor that effectively overcomes drug resistance in hematologic tumors due to c-kit gene overexpression. It is currently used for the treatment of Philadelphia chromosome-positive (Ph+) chronic granulocytic leukemia and is still in clinical trials.
.
.
Dr. Xiao Dan, Department of Hematology, South Hospital, Shanghai Renji Hospital, also contributed to this article