IMMUNOPHENOTYPING OF ACUTE LYMPHOBLASTIC- LEUKEMIA - DIAGNOSTIC ASPECTS AND CLINICAL RELEVANCE

During the past two decades immunophenotyping has yielded significant new information regarding the biological heterogeneity of ALL and has provided a solid basis for a biologically oriented and reliable classi fication of this disease. At present, lineage commitment of acute leuk aemias can be achieved in more than 98 % of cases by applying a standa rdized panel of mAbs to pan-B-cell (CD 19, cyCD 22), pan-T-cell (cyCD 3, CD 7) and pan-myeloid antigens (CD 13, CD 33, MPO) that are express ed either on the surface or in the cytoplasm of the earliest progenito rs of the respective cell lineage. Further subclassification of ALL ba sed on the analysis of antigens more closely associated with different maturational stages of B- and T-cell lineage has proven useful for th e identification of biologically and clinically distinct entities in b oth B-cell precursor and T-lineage ALL. Immunophenotyping in about 280 0 patients recruited for the German multicentre trials has shown that children and adults differ markedly in frequency distribution of immun ological subgroups, with a higher adult incidence of immature B-cell p recursor (i.e., pre-pre-B ALL) and T-lineage ALL immunophenotypes (i.e ., pre-T ALL). Detailed immunological analyses using a broad panel of mAbs have recently documented typical ALL cases inappropriately expres sing myeloid antigens (My+ ALL) as well as morphologically/cytochemica lly defined acute myeloid leukaemia (AML) with lymphoid-associated mar kers (Ly+ AML). Based on our own results and a critical review of publ ished data, leukaemic blasts in 5-20% of ALL patients disclose My+ ALL , whereas a coexpression, mostly of T-cell-associated antigens, can be identified in 10-25% of AML cases. The clinical relevance of My+ ALL and Ly+ AML is as yet unclear. Several immunophenotypic features in bo th childhood and adult ALL have been found to be associated with a poo r prognosis (e.g., pre-pre-B ALL or null-ALL, pre-B ALL, B-ALL, pre-T ALL; myeloid-antigen-positive ALL). At least in B-cell precursor ALL, however, the worse prognosis of the pre-pre-B or pre-B phenotype was a ttributed mainly to the distinct biological (e.g., chromosomal aberrat ions) and clinical features (e.g., high tumour cell load) of these sub groups, and the independent value of immunophenotyping in predicting o utcome has not yet been established. In addition, several studies have shown that more effective treatment may lessen the negative prognosti c impact of immunophenotypic features (e.g., in B-ALL).