Mixed-phenotype acute leukemia (MPAL) and beyond

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Mixed-phenotype acute leukemia (MPAL) is a rare but difficult to treat hematologic malignancy with immuno-phenotypic co-expression of at least two cell lineages, or with only rare cases involving all three lineages, e.g. myeloid with B-or T-lymphoid or all three of myeloid, Band T-lymphoid altogether. The WHO has classified MPAL as biphenotypic and bilineal leukemias as a heterogeneous category of 'acute leukemias of ambiguous lineage', but excluding the more cases with recurrent genetic abnormalities. Instead, the European Group for the Immunological Classification of Leukemia (EGIL) simply defines the MPAL by the scoring criteria for diagnosis. Therefore, there are some issues to be considered when we diagnose and treat patients with MPAL by using either the WHO or EGIL guidelines. By the EGIL criteria, biphenotypic acute leuke-mia is diagnosed when a score more than 2 points is noted for each lineage of myeloid or lymphoid. According to the literature, it is more common in adults and many reports showed poor-prognostic cytogenetics including a complex karyotype, t(9;22), and 11q23 [1]. However, this unusual but particular situation of 'MPAL' in a category of 'acute leukemias of ambiguous lineage' in 2008/2016 WHO classification is still not well known the pathobiology and appropriate treatment in clinic. Previously, it was named differently as 'biphenotype acute leukemia (BAL)' as a rare disease entity that comprises less than 3% of all acute leukemias and the optimal therapeutic approach for BAL has been unknown yet. As we may know the difference by morphologic, cytochemical and immuno-phenotypic characteristics of both myeloid and B/T-lymphoid lineages, even the scoring system for markers by the EGIL is partly useful in some ways of making an appropriate therapeutic decision. Sometimes many cases of AML at diagnosis show one or more lymphoid marker(s) as a manifestation of aberrant lineage expression together. Moreover, recent data showed that leukemia stem cells (LSCs) with lymphoid characteristics can propagate MPAL, which was resulting from several other studies showing that the MLL-ENL fusion gene or t(8;21) RUNX1/RUNX1T1 positive AML could induce lineage reassignment of T cell progenitors to generate AML [2-4]. These findings suggest that in some cases of MPAL the AML/ALL-LSCs can be initiated by malignant transformed hematopoietic stem cells, possibly during hematopoiesis of common myeloid precursors as well as common lymphoid precursors or their downstream myeloid/lymphoid progenitors. What can we do …