Objective: We examined RAS mutational status and correlated this with presenting morphology, cytogenetics, clinical outcome and other gene aberrations in a large cohort of Chinese acute myeloid leukemia (AML) patients.
Designs and methods: N-RAS and K-RAS were screened for mutations at hot-spot codons 12, 13 and 61 using high resolution melting analysis (HRMA) and direct DNA sequencing in 504 Chinese AML patients and their clinical relevance was analyzed.
Results: The frequencies of mutations of N-RAS and K-RAS were 9.7% (49/504) and 2.9% (15/504), respectively. c.35G>A (rs121913237: G>A; p.Gly12Asp and rs121913529: G>A; p.Gly12Asp) and c.38G>A (rs121434596: G>A; p.Gly13Asp and rs112445441: G>A; p.Gly13Asp) were the most common base substitutions (46% in N-RAS and 60% in K-RAS, respectively). AML patients with RAS mutations presented significantly higher white blood cell count (WBC) at diagnosis than those without mutations (p<0.001). RAS mutations were underrepresented in patients with t(15;17) (2.9%, p=0.01), while overrepresented in cases with abn11q23 (50%, p=0.002) and inv(16) (66.6%, p=0.04). In the FAB subtypes M4 and M5, RAS mutations were more frequent (21.6% and 20.6%, respectively) than they were in other subtypes (7.5%, p=0.006 and 0.005, respectively). FLT3-ITD and RAS mutation were rarely coexistent (p=0.03). RAS mutation didn't influence overall survival (OS) either in the entire cohort or within some defined subgroups.
Conclusions: RAS mutations are associated with some biologically specific subtypes of AML but don't impact clinical outcome in Chinese patients.
Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.