Abnormal in vitro differentiation of clonogenic B-cells in common acute lymphoblastic leukemia in complete remission. A marker for minimal residual disease?

An in vitro B-cell colony assay system was used to evaluate B-cell differentiation from peripheral blood precursors in common acute lymphoblastic leukemia (cALL) patients in remission as compared to normal controls. Significant differences in the morphologic and phenotypic features of pooled colony cells were found between the two groups. The morphology and surface markers of control-cultured cells were those of young plasmocytes. In contrast, patients' cells had predominantly a lymphoblastoid appearance and a mean of 18% (2-72%) of the cells expressed the cALL (CALLA) antigen. This marker, known to be present on normal pre-B-cells and malignant cALL cells, was not found on control colony cells. Cytogenetic studies performed in four cases showed that a fraction of the patients' colony cells had karyotypic abnormalities similar to that of the original lymphoblasts. These data suggest that the cells with immature features persisting in the colonies of cALL patients are the progeny of residual circulating cells linked to the malignant clone which cannot be detected in the fresh sample and are clonally expanded during the culture.