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. 2023 Apr;45(2):221-228.
doi: 10.1111/ijlh.14007. Epub 2022 Dec 11.

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

Smeeta Gajendra  1 , Ritu Gupta  1 , Deepshi Thakral  1 , Sanjeev Kumar Gupta  1 , Garima Jain  2 , Sameer Bakhshi  3 , Atul Sharma  3 , Ranjeet Kumar Sahoo  3 , Lalit Kumar  3 , Sandeep Rai  1 , Saroj Singh  1 , Ashish Datt Upadhyay  4
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CD34 negative HLA-DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3-ITD mutations

Smeeta Gajendra et al. Int J Lab Hematol. 2023 Apr.

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.

Keywords: CD34 negative HLA-DR negative AML; CD34 positive HLA-DR negative AML; DIC; FLT3-ITD; NMP1; flow cytometric immunophenotyping.

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References

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