Flow cytometry in the diagnosis of acute leukemia

Acute leukemias are a heterogeneous group of malignancies with varying clinical, morphologic, immunologic, and molecular characteristics. Many distinct types are known to carry predictable prognoses and warrant specific therapy. Distinction between lymphoid and myeloid leukemias, most often made by flow cytometry, is crucially important. Several advances in flow cytometry, including availability of new monoclonal antibodies, improved gating strategies, and multiparameter analytic techniques, have all dramatically improved the utility of flow cytometry in the diagnosis and classification of leukemia. Acute leukemias reflect the pattern of antigen acquisition seen in normal hematopoietic differentiation, yet invariably demonstrate distinct aberrant immunophenotypic features. Detailed understanding of these phenotypic patterns of differentiation, particularly in myeloid leukemia, allows for more precise classification of leukemia than does morphology alone. However, morphologic and differentiation-based classifications of leukemia are limited in their prognostic value; cytogenetics and molecular genetics appear to be most important for identifying entities with distinct prognoses and clinical behavior. Increasingly, many of these genetically distinct subgroups of leukemia have been found to be closely associated with distinct immunophenotypes. For example, translocations such as t(8;21), t(15;17), and inv(16) in acute myeloid leukemia (AML), and t(1;19) and t(12;21) in acute lymphoblastic leukemia (ALL) have distinctive immunophenotypic profiles. Thus, in addition to classification into differentiation-based subtypes, detailed flow cytometric studies can define complex antigenic profiles that are associated with specific molecular defects and well-defined biology. In summary, multiparameter flow cytometry is an invaluable tool in the diagnosis, classification, and monitoring of patients with acute leukemia.