Immunophenotyping in the diagnosis and classification of acute lymphoblastic leukemia

The identification of ALL immunophenotypes with distinctive clinical features and prognostic significance indicates the importance of these studies in the evaluation of ALL patients for both clinical and research purposes. For differential diagnosis, the expression of pan-B-cell or pan-T-cell lymphoid antigens and the absence of myeloid/monocyte antigens represent the most useful markers for distinguishing ALL from AML. However, the increasing appreciation of large numbers of patients with clinically significant mixed lymphoid-myeloid phenotypes suggests that rigid classification of acute leukemias into exclusive lymphoid and myeloid categories may be somewhat artificial. In adult ALL, patients with My+ phenotypes (B+sIg-T-My+ and B-sIg-T-My+) have a lower incidence of complete remission and shorter survival times than do patients with My- marker profiles. Preliminary studies in childhood ALL also suggest a correlation between myeloid antigen expression and poor prognostic factors. In addition, children with sIg+ "B-cell," cIg+ "pre-B-cell," and T-cell ALL phenotypes have shorter disease-free survival times than do patients with more common "early pre-B" (B+cIg-sIg-T-) marker profiles. Application of immunologic markers in concert with cytogenetic and gene rearrangement studies has led to the identification of novel subgroups of leukemia with distinct clinical characteristics. Future studies incorporating a multiparameter diagnostic approach including immunophenotyping, gene rearrangement studies, and karyotypic analyses should further our understanding of the heterogeneity of acute leukemias, guide the development of new therapeutic strategies, and provide for more clinically relevant classification of these disorders.