Karyotypically distinct subpopulations in acute leukemia with specific growth requirements.

Bone marrow and blood cells of a patient with acute monoblastic leukemia with subclones marked with specific karyotypic abnormalities were investigated. In order to more precisely evaluate the proliferative abilities of these populations, leukemic cell enriched fractions were prepared and incubated in two colony assays. Colony forming cells of the disparate clones had growth advantages in different systems which shows that their proliferation depended on the presence of selective stimulatory factors in culture. In one assay, at diagnosis, colonies from the minor clone were demonstrated exclusively. It is suggested that the assays measured distinct cellular stages of myeloid differentiation and the findings indicate that prior to diagnosis the neoplasm had evolved into subsets with progressive dedifferentiation. Differences of growth in vitro correlated with the different roles of these clones in the clinical history of the disease. Approaches based on differential cloning of tumor stem cells as in this example, may be useful for discriminating biological properties of heterogeneous subpopulations within neoplasms, and may facilitate the cytogenetic recognition of minimal clones among composite malignant cell specimens.