Immunophenotype of Acute Lymphoblastic Leukemia Cells: The Experience of the Italian Cooperative Group (Gimema)

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Abstract
The immunophenotype of 304 adult lymphoblastic leukemias (> 18 years) diagnosed on the basis of the FAB criteria was determined at the time of diagnosis using a panel of monoclonal antibodies. The series comprised cases diagnosed and immunophenotyped in 43 Italian centers (GIMEMA Cooperative Group) between April 1988 and June 1991. The immunophenotypic characterization consisted of two consecutive steps. The initial screening was based on the reactivity for Tdt, HLA-Dr, CD7, CD10, CD13, CD19, CD24, CD33 and CD41. According to the results obtained, the second level of investigation assessed the positivity for intra cytoplasmic (Cy) Ig, CD la, CD2, CD3, CD4, CDS, CDS and CD20. Based on the hierarchial expression of the different B- and T-cell related antigens, each case was assigned to a given differentiation stage. B-lineage ALL were classified in five subgroups (B0-B4) and T-lineage ALL in four subgroups (T0-T3). Cases in which the blasts were lymphoid according to the FAB criteria, but expressed myeloid antigens in association with B- and T-lymphoid markers were defined as hybrid leukemias. As expected, CD10 + cases (B2-B3) were the most frequent within the B-lineage ALL (83.2% of cases). Cylg+ (B3) accounted for about 20% of CD10+ ALL. Twenty eight cases (13.4%) were at a pre-cALL stage (B0-B1) and of these, 8 (3.8% of the total series) were positive only for TdT and HLA-Dr (BO). Intermediate and mature thymic phenotypes (T2-T3) were predominant within the T-ALL (67.2%) groups. Five cases, were positive only for TdT and CD7 (CD5 +), and classified as T0. 9.2% of cases fulfilled the definition of hybrid leukemia, largely in view of the co-expression of B-lymphoid and myeloid markers. In most cases the cells were at a B2 stage of differentiation. Analysis at the DNA level, carried out in 6 cases, showed that all had a monoclonal rearrangement of the Ig heavy chain gene, sometimes coupled with concomitant TCR gene rearrangement. Mediastinal enlargement was found in 38.9% of the T-ALL cases, but was undetectable in the other subgroups. Anemia was more pronounced in B-lineage ALL while high WBC counts were more frequent in T-ALL., where a greater tumor load was documented. Overall, only 7 cases (2.3%) diagnosed as ALL on the basis of the FAB criteria were re-classified as AML after immunologic characterization. The diagnostic role of phenotypic and genotypic analyses is discussed.