Screening of C坼kit gene Mutation in Acute Myeloid Leukaemia in Northern India

作者：Hussain SR; Raza ST; Babu SG; Singh P

来源：Iranian Journal of Cancer Prevention, 2012.

• Proto-Oncogene proteins c-kit
• Acute Myeloid Leukaemia
• Mutation
• Polymerase Chain Reaction
• Single-Stranded Conformational Polymorphism

Background: Acute Myeloid Leukaemia (AML) is a cancer of blood-forming cellsin bone marrow. C-kit gene is a Receptor Tyrosine Kinase class III (RTK) that isexpressed by early hematopoietic progenitor cells and plays an important role inhematopoietic stem cell proliferation, differentiation and survival. It is known thatc-kit is a proto-oncogene and the activating c-kit mutations are likely to contributein the development of leukaemia in humans. Exon 11 of c-Kit gene is the frequentsite for mutations in different kinds of tumours.Methods: In order to determine the frequency and prevalence of exon 11mutations in 51 AML cases, we have done polymerase chain reaction-single-strandconformational polymorphism followed by direct DNA sequencing.Results: The c-kit mutations in exon 11 were detected in 15.68% (8/51) in AMLcases. We have detected totally ten missense mutations in eight AML cases thoseinclude Lys550Asn, Tyr568Ser, Ile571Leu, Tyr578Pro, Trp582Ser andArg588Met and novel missense mutations at codons Ile563Lys and Val569Leu.Mutations at codons Ile571Leu and Trp582Ser was found in two independentcases.Conclusion: The presence of c-kit mutations in our study adds to investigativespectrum of AML cases. Since the c-kit mutations are seen in other malignancies,mutations in exon 11 of the c-kit gene might be involve in pathogenesis andrepresent useful predictive genetic marker in AML. Further studies in larger groupof cases possibly will be required to determine the prognostic implications and toinvestigate how these mutations are co-related to the progression andpathogenesis of AML.