The International Consensus Classification of Acute Leukemias of Ambiguous Lineage
Olga K. Weinberg, Daniel A. Arber, Hartmut Döhner, Charles G. Mullighan, Etan Orgel, Anna Porwit, Richard M. Stone, Michael J. Borowitz
Abstract
The International Consensus Classification of Myeloid and Lymphoid Neoplasms is the result of the findings of a clinical advisory committee (CAC) meeting with involvement by an international group of hematologists, oncologists, pathologists, and geneticists. 1,2The formal CAC meeting, however, did not address potential changes to the classification of acute leukemias of ambiguous lineage (ALAL); a CAC subgroup was created to address this issue (Table 1).ALAL include biologically diverse leukemias that fail to show commitment to either the myeloid or lymphoid lineages or show evidence of commitment to more than 1 lineage. [1][2]2][3] Cases in the former group are referred to as acute undifferentiated leukemias (AUL), whereas those in the latter are identified as mixed-phenotype acute leukemias (MPAL).One of the major challenges in the subclassification of ALAL in general and MPAL in particular is that classification based primarily on driver mutations does not explain the phenotypic diversity seen in these leukemias.Although we anticipate that future generations of leukemia classification will recognize that these are better considered as single entities with variable expression of differentiation-related markers, because the highest-level organizing principle of current classification is phenotypic, and because current clinical protocols still require distinction between MPAL and single-lineage leukemias, distinguishing MPAL from leukemia of a single lineage with the same genetic driver requires an immunophenotypic definition.