Abstract
The topology of mutations in persons of predominately European-descent with acute myeloid leukaemia (AML) is reasonably well-described. We studied the topology of AML-related mutations in 289 consecutive Chinese (mostly Han) with newly-diagnosed de novo AML. Full-length coding sequence of NPM1 and CEBPA, IDH1 and IDH2 hotspot mutations and WT1 mutations in exons 7 and 9 were analyzed by PCR. We also interrogated correlations between mutations and clinical and laboratory variables including age, sex, leukaemia type, cytogenetics, WBC and platelet levels and percent bone marrow blasts. CEBPA mutations were detected in 49 subjects (20%; 95% confidence interval [CI] 15.25, 25.41%). Of these 7% (4.14, 10.78%) were mono-allelic and 13% (8.63, 17.09%), bi-allelic. NPM1 mutations were detected in 20% (15, 25%) of subjects. IDH1 mutations were detected in 4% (1, 6%) of subjects. IDH2 mutations were detected in 11% (7, 15%) of subjects. WT1 mutations were detected in 6% (3, 9%) of subjects. There was no concordance for IDH1 and IDH2 mutations. 6 subjects with a NPM1 mutation also had an IDH1 mutation (P <0.05) and 11 also had an IDH2 mutation (P <0.001). A comparison of these data with published mutation frequencies in persons of predominately European-descent with AML indicate a higher frequency of CEBPA mutations, a similar frequency of IDH2 mutations and lower frequencies of NPM1, IDH1 and WT1 mutations. In Chinese with AML, CEBPA mutations were correlated with lower platelet levels and percent bone marrow blasts compared with subjects without these mutations. NPM1 mutations were correlated with older age and higher WBC and platelet levels. IDH2 mutations were also correlated with older age and higher platelet levels. We found no significant correlation between mutations in IDH1 or WT1 and any of the clinical or laboratory variables we tested. Our data indicate a different topology of common AML-associated mutations in Chinese compared with persons of predominately European-descent suggesting genetic background, life-style, environment and possibly other variables may influence likelihood of developing AML amongst Chinese. There are also implications for the potential impact of therapies targeting these mutations in different populations.
No relevant conflicts of interest to declare.
