Oddballs: acute leukemias of mixed phenotype and ambiguous origin

From the standpoint of the hematopathologist, attempts to dissect the immunophenotype and other lineage-defining characteristics of the puzzling group of acute leukemias of ambiguous origin have prompted considerable discussion and debate. For clinicians, however, such definitions, although academically interesting, as yet give relatively little insight into the most appropriate therapy, and patients with MPAL continue to do poorly compared with more typical AML or ALL cases. The most recent WHO 2008 MPAL definitions are provocative, but represent a major change from the previous EGIL BAL classification, and the clinical relevance of this change has yet to be established. Only further insight from the molecular biology laboratory can help define the true cell of origin and molecular drivers of ambiguous leukemias. New molecular information will allow clinicians and pathologists to refine classification of these challenging entities, and most importantly, should permit improved treatment for patients.