Abnormal in vitro differentiation of peripheral blood clonogenic B cells in common acute lymphoblastic leukemia...

An in vitro B cell colony assay system was used to evaluate B cell growth from peripheral blood precursors in common acute lymphoblastic leukemia (CALL) patients in remission during maintenance therapy and in normal controls. Major differences between the two groups were found in the phenotypic and morphologic features of pooled colony cells. In both cases, the cells were E-. Controls' cells were surface immunoglobulin (sIg)-positive, and some (mean, 25%) expressed la determinants. By Wright-Giemsa staining, they appeared as plasmacytoid cells. In contrast, patients' cells had predominantly a lymphoblastoid appearance, fewer cells had developed sIg, and a large fraction (mean, 43%) were Ia-positive. Moreover, the CALL antigen (CALLA) was expressed by a mean of 18% (range, 2% to 72%) of the patients' colony cells, whereas CALLA was never found in control colonies. Thus, cells with immature features persist in the colonies of CALL patients. Secondary colonies could be generated from the patients' cultured cells, indicating their self-renewal capacity. CALLA + cells were also present in the secondary colonies. Finally, cytogenetic studies showed that a fraction of the patients' colony cells had karyotypic abnormalities similar to that of the original lymphoblasts. It is believed that in CALL patients this B cell assay permits the clonal expansion of residual circulating cells linked to malignant clones that are not detectable by classic hematologic and cytologic methods.