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

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.

A Real-world Perspective of CD123 Expression in Acute Leukemia as Promising Biomarker to Predict Treatment Outcome in B-ALL and AML.

INTRODUCTION: CD123 is overexpressed in many hematologic malignancies and found to be useful in characterizing leukemic blasts of both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 has been recently found to be a marker of leukemic stem cells, and its utility to measure residual disease and potential role in disease relapse is under evaluation. MATERIALS AND METHODS: Herein, we have evaluated the expression of CD123 in 757 samples of acute leukemia including 479 treatment-naive and 278 follow-up samples and compared with post-induction morphologic complete remission and measurable residual disease (MRD) status. Multiparametric flow cytometry was used for assessment of CD123 expression and immunophenotypic characterization of leukemic blasts at diagnostic and MRD assessment time points. RESULTS: Using variable cutoffs of 5%, 10%, and 20% to define a case as CD123-positive, expression of CD123 was observed in 75.6%, 66.2%, and 50% of AML and 88.6%, 81.8%, and 75% of B-ALL, respectively. Of 11 patients, 7 (63.63%) had mixed phenotype acute leukemia, but none of the 12 patients with T-acute lymphoblastic leukemia showed positivity for CD123. CD123 expression at diagnosis was associated with post-induction MRD-positive status in both B-ALL (P < .001) and AML (P = .001). We also evaluated the utility of CD123 as a leukemia-associated aberrant immunophenotype and found it to be useful in both patients with AML (baseline, 50.6%; follow-up, 53%) and B-ALL (baseline, 75%; follow-up, 73.07%). CONCLUSIONS: In conclusion, CD123 may be considered as a cardinal marker for residual disease assessment and response evaluation in AML and B-ALL.