[Frequency and clinical features of ASXL2 gene mutation in acute myeloid leukemia patients with AML1- ETO fusion gene positive].

Objective To investigate frequency and clinical features of additional sex combs-like 2 (ASXL2) gene mutation in acute myeloid leukemia (AML) patients with AML1-ETO fusion gene and to analyze the relationship between ASXL2 gene mutation and c- kit gene mutation. Methods Mutation analysis of exon 11 and 12 of ASXL2 gene in 59 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis. The clinical features, survival curve and c-kit gene mutation in ASXL2 gene mutation positive and negative patients were compared. Results In a total of 59 AML patients with AML1-ETO fusion gene positive, 11.9% (7/59) patients harboured ASXL2 gene mutations. The hemoglobin levels of patients with mutated ASXL2 gene [56.2 (38.0- 72.0) g/L] were significantly lower than those with wild type ASXL2 [69.0(37.2-154.0) g/L] (P=0.038). Differences were not observed in white blood cell counts, platelet counts, the proportion of acidophilic cell, and the proportion of primitive cell in the marrow between patients with mutant ASXL2 and ones without mutant ASXL2 (P>0.05). None of all 59 patients suffered from liver, spleen, central nervous system metastases in both groups. Moreover, enlarged lymph nodes was similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P=0.859). Immunophenotypic analysis: in positive group CD33 positive expression was significantly lower than that of negative group (P=0.033). cCD3 was not expressed in both groups. Expression levels of CD117, cMPO, HLA-DR, CD34, CD38, CD13, CD44, CD15, CD64, CD11b, CD56, CD19, cCD79a and CD7 were similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P>0.05). All of 59 patients were in remission (P=0.577). Overall survival was similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P=0.631). The mutation rates of c- kit in positive group and negative group were 14.3% and 29.4%, without statistical significance (P= 0.697). Conclusions ASXL2 mutation may be a new event that can cooperate with AML1-ETO to induce leukemia. Patients in AML1- ETO positive AML with ASXL2 mutation show specific clinical characteristics of hemoglobin levels and expression level of CD33. ASXL2 gene mutations and c-kit gene mutations may not have a specific correlation between them. Key words: Leukemia, myeloid, acute; Gene, ASXL2; DNA mutation