Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification

The t(12;21)(p13;q22) fusion gene is the most frequent genetic lesion descr ibed in precursor B cell acute lymphoblastic leukemia (ALL) of childhood oc curring in a quarter of cases. This gene rearrangement is associated with a good outcome presenting a high response rate to chemotherapy. In spite of its potential clinical relevance, the t(12;21) translocation usually goes u ndetected with conventional cytogenetic procedures. In the present study we utilized an objective flow cytometric approach (multiparametric quantitati ve analysis) for the phenotypic characterization of this type of ALL. We st udied a total of 74 precursor B-ALL children, including 21 t(12;21)(+) and 53 t(12;21)(-) cases. Our results show that the t(12;21)(p13;q22)(+) ALLs d isplay a higher intensity of CD10 (P = 0.0016) and HLADR (P = 0.005) expres sion together with lower levels of the CD20 (P = 0.01), CD45 (P = 0.01), CD 135 (P = 0.003) and CD34 (P = 0.03) antigens as compared to the t(12;21)- c ases. Moreover, as regards CD34 expression, we observed a more heterogeneou s antigen expression within individual patients with higher coefficients of variation (median of 202 vs 88, P = 0.0001). A multivariate analysis discl osed that with the immunophenotypic approach used identification of t(12;21 )(+) cases can be achieved with a sensitivity of 86% and a specificity of 1 00%. We conclude that childhood precursor B-ALL carrying the t(12;21) trans location display characteristic phenotypic features which could provide a r apid, simple, sensitive and specific screening method to select for those c ases that should undergo confirmatory molecular analysis.