Human Leukocyte Antigen-DR and Cluster Designation 34: Double-negative Acute Myeloid Leukemias – Our Experience in Clinical Setting

Abstract

Abstract Introduction: Dual negativity for cluster designation (CD) 34 and human leukocyte antigen (HLA)-DR antigen in leukemia panel is an important finding in clinical practice. The combination of this finding though seen classically in acute promyelocytic leukemia (APL) is not specific to it but can be seen in many other myeloid leukemias like the ones associated with nucleophosmin 1 (NPM1) or FMS-related tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) abnormalities. It is important to identify APL from non-APL leukemia as treatment and prognosis vary. Aims and Objectives: We analyzed CD 34 and HLA-DR dual-negative acute myeloid leukemia (AML) cases presented to us over 2.5 years (26 cases) and segregated them into APL and non-APL groups to study their morphological/flow cytometric and cytogenetic profile and correlation with treatment response. Materials and Methods: It was a prospective study including all newly diagnosed AMLs showing CD 34 and HLA-DR dual negativity in flow cytometry profile. Cases in which complete information/cytogenetics/molecular profile were not available, were excluded from the study. The patients were followed up till the end of induction to look for morphological response to induction therapy. The clinical and treatment records were pulled out from the patient database after ethical committee clearance. Results: A total of 139 new AML cases were encountered during the study period out of which 28 (20%) were found to be dual negative for CD34 and HLA-DR. The non-APL group showed higher mean age, TLC at baseline, variable morphology, and more number of aberrant expression on flow cytometry profile. No significant difference was noted in terms of gender, presence of hepatosplenomegaly, DIC as complication, or percentage of blasts/blasts equivalent at baseline. Our study found that while all APL patients had PML-RARA, the associated molecular abnormalities were much lesser as compared to the non-APL group which showed a variety of abnormalities such as NPM1, FLT3, RAS mutation, and mutations involving epigenetic modifiers. The response rate to induction therapy was significantly lower in the non-APL group as compared to the APL group. Conclusion: The non-APL myeloid leukemia which is dual negative is commonly found to be associated with cup-shaped morphology, NPM, or FLT3-ITD mutation along with other abnormalities. These patients were older in age, showed higher TLC and higher blast counts, associated with poorer response to induction therapy as compared to the APL group.