Lack of KRAS Gene Mutations in Chronic Myeloid Leukemia in Iran

Mohammad Mahdi Kooshyar,Maryam Sheikhi,Mohammad Hadi Sadeghian,Mohammad Reza Keramati,Mohsen Miri,Hossein Ayatollahi

doi:10.7314/apjcp.2013.14.11.6653

Mohammad Mahdi Kooshyar, Maryam Sheikhi + Show 4 more

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https://doi.org/10.7314/apjcp.2013.14.11.6653

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Abstract

The single most common proto-oncogene change in human neoplasms is a point mutation in RAS genes. A wide range of variation in frequency of KRAS mutations has been seen in hematologic malignancies. Despite this, RAS roles in leukemogenesis remain unclear. The frequency of KRAS mutations in CML has been reported to be between zero an 10%. Many attempts have been done to develop an anti-RAS drug as a therapeutic target. . This cross sectional study was performed in Mashhad University of Medical Sciences, Mashhad, Iran from 2010-2012. In 78 CML patients (diagnosed according to WHO 2008 criteria) in chronic or accelerated phases, KRAS mutations in codons 12 and 13 were analyzed using a modified PCR- restriction fragment length polymorphism (RFLP) method. We did not detect any KRAS mutations in this study. KRAS mutations are overall rare in early phase CML and might be secondary events happening late in leukemogenesis cooperating with initial genetic lesions.

Highlights

A neoplasm is created by the clonal proliferation of a precursor cell with genetic damage
KRAS mutations are overall rare in early phase chronic myeloid leukemia (CML) and might be secondary events happening late in leukemogenesis cooperating with initial genetic lesions
The RAS protein is activated in many hematopoietic growth factor signaling and in hematologic neoplasms and a wide range of variation in frequency of RAS mutations have been observed in hematologic neoplasms (Ahuja et al, 1990; Braun et al, 2004); RAS role in leukemogenesis is not completely clear (Baum and Ren, 2008)

Summary

Introduction

A neoplasm is created by the clonal proliferation of a precursor cell with genetic damage. In the inactive form, it binds GDP, but cell Stimulation by growth factors cause, inactive (GDP-bound) form is activated to a GTP-bound state. Activated RAS stimulates RAF and mitogen-activated protein (MAP) kinase cascade to transmit growth signals to the nucleus (Chan et al, 2004; Stricker et al, 2010). RAS has a basic role in signal transmission of growth factor receptors within cytoplasm and the activated form stimulates downstream regulators of proliferation. The RAS protein is activated in many hematopoietic growth factor signaling and in hematologic neoplasms and a wide range of variation in frequency of RAS mutations have been observed in hematologic neoplasms (Ahuja et al, 1990; Braun et al, 2004); RAS role in leukemogenesis is not completely clear (Baum and Ren, 2008). In this study we assessed the frequency of KRAS mutation (codon 12, 13) in CML

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