Kotrova M, Musilova A, Stuchly J, Fiser K, Starkova J, Mejstrikova E, Stary J, Zuna J, Hrusak O, Trka J, Zaliova M. Blood. 2016 Nov 3;128(18):2263–2266. Epub 2016 Sep 13. IF: 11.847
MUDr. Michaela Kotrová, Ph.D., Department of Paediatric Haematology and Oncology
Letter to the Editor:
Mixed phenotype acute leukemias (MPAL) are a rare subset of acute leukemias that cannot be unambiguously assigned to a single hematopoietic lineage due to the significant expression of antigens from additional lineages. This subset comprises several entities, including biphenotypic leukemias, in which leukemic blasts co-express markers of two lineages, and bilineal leukemias (BLL), which demonstrate two immunophenotypically distinct populations, each belonging to a different lineage. These two entities may overlap significantly. Proper treatment of MPAL is still an undecided question that can be addressed by combining international clinical experience with biological knowledge.
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In summary, utilizing complex genomic analyses, we did not identify any genetic aberrations that were specifically present in only one of the immunophenotypically distinct subpopulations in either of the two cases investigated upon the diagnosis of BLL. Although we cannot exclude that such aberrations triggering the immunophenotypic lineage split (or contributing to it) do exist in certain BLLs, this does not appear to be a general mechanism, at least in T/myeloid BLL. Conversely, mutational analysis of WT1 in patient 2279 suggests that lineage plasticity is inherent to the vast majority of leukemic blasts, which alter their transcriptional programs and differentiate into different lineages in a stochastic manner. Our results shed new light on BLL: not only can all immunophenotypically heterogeneous leukemic populations be derived from an identical founder cell, but multiple leukemic cells possess the potential to differentiate into very distinct cell types. Further studies employing large case cohorts are needed to elucidate whether this lineage plasticity in BLL associates with certain specific genetic and/or epigenetic backgrounds.
