A study of KIT activating mutations in acute myeloid leukemia M0 subtype in north India

AbstractAcute Myeloid Leukemia (AML)-M0 is a cancer of blood-forming cells in the bone marrow. KIT gene is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. We have designed this study aiming to identify and determine the frequency and prevalence of mutations in North Indian patients suffering from AML-M0. To perceive the KIT gene mutations, we have carried out PCR–SSCP followed by direct DNA sequencing in 50 AML-M0 cases. We have found eight cases (24.2%) with t(8;21) having 12 point mutations whereas three cases (17.6%) with inv(16) having four point mutations. The point mutation detected at exon 9 in five cases is Asp496Val. Eight different point mutations were identified at exon 11 in seven AML-M0 cases that include Lys550Asn, Tyr568Ser, Ile571Leu, Tyr578Pro, Trp582Ser and Arg588Met. Point mutations at codons Ile571Leu and Trp582Ser was found in two independent cases. Three point mutations were found in exon 17 (Leu813Pro, Lys818Arg, Val825Ala) in three AML-M0 cases. The results underline that the KIT gene appears to be most frequently mutated target in AML-M0 cases. These observations suggest that mutations in exon 11 of the KIT gene might be useful molecular genetic markers in AML-M0 and these mutations might be related to progression and clinical pathogenesis