CD34 negative HLA‐DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3‐ITD mutations

Abstract Introduction CD34 and HLA‐DR negativity is often used as a characteristic immunophenotypic feature of acute promyelocytic leukaemia (APL) that differentiates APL from other subtypes of acute myeloid leukaemia (AML). However, other subtypes of AML, without expression of CD34 and HLA‐DR antigens, have also been reported. Methods We analysed the HLA‐DR negative de novo non‐APL AML cases by dividing HLA‐DR negative non‐APL group into 2 sub‐groups based on CD34 expression and compared the characteristics of CD34 negative HLA‐DR negative with CD34 positive HLA‐DR negative non‐APL AML cases with respect to morphologic, immunophenotypic, molecular and clinical parameters. Results There were 70 cases (8.54%) which were CD34 negative HLA‐DR negative and 52 cases (6.34%) were CD34 positive HLA‐DR negative. The median age at diagnosis was higher in CD34 negative HLA‐DR negative AML than in CD34 positive HLA‐DR negative AML group (38 years vs. 12 years, p < 0.001). DIC rate was higher in CD34 negative HLA‐DR negative group than the other group ( p < 0.001). Median total leucocyte count was higher with higher blast count in peripheral blood and bone marrow in CD34 negative HLA‐DR negative AML cases than the other group ( p < 0.05). CD34 negative HLA‐DR negative AML was more associated with normal karyotype (96.2% vs. 38.5%; p < 0.001), NPM1 mutation (67.8% vs. 8.3%; p < 0.001) and FLT‐ITD mutation (37.3% vs. 13.9%; p < 0.05). In CD34 negative HLA‐DR negative group, 16 cases had co‐occurrence of NPM1 and FLT3‐ITD mutations, whereas no case of CD34 positive HLA‐DR negative group had such dual mutation positivity. There was poor median overall survival [3.8 months (95%CI: 2.3–7.8 months) vs. 20.4 months (95% CI: 12.8–25.7 months); p = 0.0148] in CD34 positive HLA‐DR negative AML than CD34 negative HLA‐DR negative AML cases. Conclusion We found that the CD34 negative HLADR negative non APL AML is highly associated with NPM1 and FLT3‐ITD mutation, older age at diagnosis, DIC, higher total leucocyte count, higher blast counts and normal karyotype in comparison to CD34 positive HLA‐DR negative AML group. Co‐occurrence of NPM1 and FLT3‐ITD mutation was also exclusively seen in CD34 negative HLA‐DR negative group. There was poor overall survival in CD34 positive HLA‐DR negative AML than CD34 negative HLA‐DR negative AML cases.