Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation

Abstract

Objectives To investigate clinicopathological and molecular features of NPM1‐mutated acute myeloid leukemia that presented with infrequent acute promyelocytic leukemia (APL)‐like phenotype and clinical presentation. Methods Cases with both de novo or secondary Acute Myeloid Leukemia (AML) were retrieved. Data from flow cytometry immunophenotyping, cytogenetics, molecular studies, and clinical presentation were analyzed. Results Cases presented with abnormal coagulation parameters and low platelets count; four of them showed a DIC index compatible with overt DIC. Two cases showed Auer rods. In all cases, immunophenotypes mimicked APL: blasts expressed CD33, CD13, and cytoplasmic MPO but did not express CD34, HLA‐DR, or CD11b. Notably, CD4 expression was observed in all cases. Neither t(15;17) nor PML/RARα gene rearrangement was detected. NPM1 gene mutation was identified in all cases. In four cases, TET2 or IDH2 co‐mutations were identified. Conclusions Our findings provide additional evidence of association between NPM1‐mutated AML with TET2 or IDH2 co‐mutations and the APL‐like immunophenotype. This AML subset was found to exist in both de novo and secondary AML. High WBC count and blasts with low to moderate side scatter and significant expression of CD4 are observed features that could assist in the differential diagnosis with APL. The occurrence of significant elevated D‐dimer levels, or even overt DIC observed at diagnosis in these cases could be relevant for this AML subtype.

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

“…They also found that the leukaemic cell counts of bone marrow was higher in HLA-DR negative non-APL than in HLA-DR positive non-APL group. Similarly, Rosainz et al 22…”

“…They also found that the leukaemic cell counts of bone marrow was higher in HLA‐DR negative non‐APL than in HLA‐DR positive non‐APL group. Similarly, Rosainz et al 22 presented five cases of NPM1 mutated that exhibited APL‐like immunophenotypes and clinical presentation with deranged coagulation parameters which is frequently associated with APL. In comparison to these studies, we had subdivided the HLA‐DR negative AML group on the basis of CD34 expression and found that CD34 negative group was more associated with DIC with no significant expression of CD19 in both groups.…”

On the distinction between acute leukemia with mutated NPM1 and acute promyelocytic leukemia by flow cytometry

“…Dear Editors, In a recent article, Arana Rosainz et al 1 present the diagnostic challenges that may arise in the phenotyping of acute myeloid leukemia (AML) when CD34 is not expressed by the blastic population.…”

Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

“…However, in some cases of AML with cytological characteristics closely resembling M3 or M3v FAB morphology, no RARA rearrangement can be detected. This group of RARA -negative AML with APL-like morphological features is either associated with other RAR family genes rearrangements such as RARB and RARG [ 2 ] or lacks any RAR rearrangements at all [ 5 , 15 ]. The diagnosis of these AML types is difficult, and therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) is not effective due to the lack of specific drug binding sites [ 1 , 16 ].…”