What is the role of immunophenotyping in the diagnosis of acute leukemias of ambiguous lineage (ALAL)?

Updated: Jun 18, 2020
  • Author: Enrique Ballesteros, MD; Chief Editor: Aliyah R Sohani, MD  more...
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The diagnosis of acute leukemia of ambiguous lineage (ALAL) is based on immunophenotyping—primarily, flow cytometric immunophenotyping, although immunohistochemistry and/or cytochemistry may also play important roles in characterization (see Table 1 under the Overview section). [1, 7, 8]

Acute undifferentiated leukemias (AULs) typically express no more than one surface membrane antigen of any given lineage. By definition, they lack T-cell–specific, myeloid-specific, and B-lineage–specific markers, as well as other lineage-specific markers (eg, those for plasmacytoid dendritic cells, erythroid precursors, and megakaryocytes). AULs are negative for MPO and the esterases by enzyme cytochemistry. The blasts often express CD34, CD38, TdT and/or HLA-DR, and may express TdT and/or CD7, none of which are considered lineage-specific.

The mixed phenotype acute leukemias (MPALs) with t(9;22)(q34;q11.2) (or BCR-ABL1 rearrangement) are most often composed of myeloblasts and B-lymphoblasts, although some have myeloblasts and T-lymphoblasts, and others even have three components (ie, myeloblasts, B-cell lymphoblasts, and T-cell lymphoblasts). The MPALs with t(v;11q23) (or KMT2A (MLL) rearrangement) are most often composed of lymphoblasts with the following immunophenotypes: CD19+, CD15+, CD20-, CD10-, and HLA-DR+, as well as a myeloblast component with monocytic differentiation (ie, monoblasts). In rare cases, a more mature immunophenotype with surface light chain expression may be seen; in these cases, there is no evidence of a c-myc rearrangement. [9, 10] The MPALs (B/myeloid and T/myeloid) may be biphenotypic or of mixed lineage.

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