Expression Of Lineageforeign Antigens In Acute Leukemia

Before an antigen expression pattern should be considered biphenotypic, the first and foremost prerequisite is that lineage affiliation be based on the overall immunophenotypic findings and not on morphology. The WHO classification proposal still includes the subtype "Acute leukemia, biphenotypic"77,78 and has adopted the EGIL (European Group for the Immunological Characterization of Leukemias) guidelines for their immunologic definition.79 Their scoring system ignores the fact that the majority of antigens are no longer understood as lineage-specific. As a result, if it is applied verbatim, scores high enough to qualify as biphenotypic leukemia are easily reached, particularly in ALL. To further complicate EGIL criteria, arbitrary cutoff points of 20 percent for most antigens and of 10 percent for myeloperoxidase, CD3, CD79a, and TdT are suggested to define the positivity of a leukemic cell population for a given antigen. This recommendation is of greatest concern,80 particularly because there is no emphasis on gating procedures, which would ensure that antigen expression data refer exclusively to the blast cell population.

The immunophenotypic criteria for defining leukemic entities coexpressing myeloid and lymphoid antigens recently set forth by Campana and Behm81 represent more closely our current understanding of leukemia immunobiology. Immun-odiagnosis is based on the finding of defined immature (myeloperoxidase, cytoplasmic CD3, or cytoplasmic CD22) or mature (cytoplasmic or surface immunoglobulin, surface CD3) lineage-specific antigens. In the presence of a lineage-determinant antigen, expression of two or more antigens from another lineage does not alter the basic immunodiagnosis. Given that the prognostic significance of lineage-foreign antigen expression in the adult acute leukemias has yet to be determined, it is best to describe leukemias according to the observed pattern of antigen expression (e.g., CD7+ AML, CD33+, CD13+ Early Pre-B ALL), so that retrospective outcome analyses can eventually be performed. The term "true mixed-lineage" or "bilineage" leukemia must be reserved for those rare cases that concomitantly express lineage-specific antigens from more than one cell lineage, more commonly in distinct leukemic subpopulations. In several such cases, cyto-genetic or molecular studies have provided evidence for a common leukemic progenitor cell for both the myeloid and lymphoid component (identical cytogenetic abnormalities or gene rearrangements). Whether or not there are prognostic implications associated with this type of antigen presentation per se is unclear. However, certain genetic defects with well-established prognostic significance that affect stem cells with multipotent differentiation capabilities, such as t(4;11) or t(9;22), may have an increased tendency to present as bilineage leukemias.82

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