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Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non- Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.

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.