RAS mutation analysis in a large cohort of Chinese patients with acute myeloid leukemia.

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.