Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?

Abstract

Purpose of Review Recent advances in the small field of the rare mixed phenotype acute leukemias (MPAL) are presented focusing on a better understanding of their pathophysiology and search for better therapeutic approaches. Recent Findings Three aspects of respective classification, therapy, and immunophenotype of MPAL are reviewed. New proposals have been made to segregate MPAL subtypes based on their genomic landscape. In parallel, it was found that a large array of therapeutic approaches has been tested in the past few years with increasingly good results. Finally, we explored the use of unsupervised flow cytometry analysis to dissect subtle variations in markers expression to better characterize the variegating aspect of MPALs. Summary Genomic and immunophenotypic aspects more clearly link MPAL subtypes with bona fide acute myeloblastic of lymphoblastic leukemias. This is likely to impact therapeutic strategies, towards a better management and outcome.

Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPALisoMPO is distinct from other MPAL subtypes

“…To the best of our knowledge, this is the first study to investigate the clinical significance of isolated dim MPO expression in adult B/myeloid MPAL using the 2016 WHO classification, specifically the pattern of heterogenous antigen expression and intensity of MPO MPAL diagnosis is challenging because of the rarity of the disease, immunophenotypic diversity, and evolving diagnostic criteria. [1][2][3][4] The expression of MPO has been recognized as a specific marker of ently contradictory conclusions as to whether these entities are within the spectrum of B-ALL 8,9 or MPAL. 7 Our study assessed clinical and pathologic findings in adult patients with B/myeloid MPAL isoMPO and indicated that the clinical outcome of patients with B/myeloid MPAL i-soMPO was similar to patients with B-ALL but better than patients with other MPAL subtypes; B/myeloid MPAL isoMPO is thus better considered within the spectrum of B-ALL.…”

“…MPAL diagnosis is challenging because of the rarity of the disease, immunophenotypic diversity, and evolving diagnostic criteria 1–4 . The expression of MPO has been recognized as a specific marker of myeloid/non‐monocytic lineage by the 2008 WHO classification.…”

“…MPAL diagnosis remains challenging because of the rarity of the disease, wide phenotypic and genomic diversity, and evolving diagnostic criteria. [1][2][3][4] The 2008 World Health Organization (WHO) classification of MPAL differs from the European Group for the Immunological Classification of Leukemias (EGIL) criteria by placing a greater emphasis on myeloperoxidase (MPO) positivity for assigning myeloid (non-monocytic) lineage and requiring that cases with recurrent cytogenetic changes or prior chemotherapy be reclassified as acute myeloid leukemia (AML). 1,5 The expression of MPO is recognized as a specific marker of myeloid lineage and is therefore considered definitive evidence of myeloid differentiation.…”

“…Mixed phenotype acute leukemia (MPAL) is uncommon and composes 1% to 5% of newly diagnosed acute leukemias. MPAL diagnosis remains challenging because of the rarity of the disease, wide phenotypic and genomic diversity, and evolving diagnostic criteria 1–4 . The 2008 World Health Organization (WHO) classification of MPAL differs from the European Group for the Immunological Classification of Leukemias (EGIL) criteria by placing a greater emphasis on myeloperoxidase (MPO) positivity for assigning myeloid (non‐monocytic) lineage and requiring that cases with recurrent cytogenetic changes or prior chemotherapy be reclassified as acute myeloid leukemia (AML) 1,5 …”

Myeloperoxidase‐positive bilineal mixed phenotype acute leukemia (B/T) with chromosome copy neutral loss of heterozygosity exhibits simultaneous diffuse leukemic infiltrations in the lung, bone, and endorachis

“…7 B/T MPAL is exceptionally rare, consisting of 5% of MPAL. 8 As a specific marker for myeloid lineage, MPO is seldomly expressed in lymphoid leukemia, let alone in B/T MPAL. 1,5 Disseminated leukemic infiltrations across the body are unwonted.…”