Acute lymphoblastic leukemia and non-Hodgkin's lymphoma of T lineage: colony-forming cells retain growth factor (interleukin 2) dependence.
The regulatory role of interleukin 2 (IL 2) in the proliferation of T acute lymphoblastic leukemia (T-ALL) and T non-Hodgkin's lymphoma (T-NHL) cells from six individual patients was analyzed in a colony culture system to which pure recombinant IL 2, and the lectin phytohemagglutinin (PHA) or the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA), had been added. The proliferative response was correlated with the inducibility of receptors for IL 2 on the surface membrane of T-ALL and T-NHL cells by incubation with TPA or PHA for 18 hours. Leukemic T cell colonies, identified by immunophenotyping or cytogenetic analysis, appeared in vitro following TPA and IL 2 stimulation in all six cases. Accordingly, receptors for IL 2, initially absent from the cell surface, were found on high proportions of the T-ALL and T-NHL cells after in vitro exposure to TPA. In contrast, colony formation stimulated by PHA and the induction of IL 2 receptors by PHA were limited to the one case of T-NHL with the mature thymocyte immunophenotype. The cells from the other patients, expressing common or prothymocyte phenotypes, did not respond to PHA. No colonies were formed in any of these cases when PHA or TPA was withheld from the IL 2-containing cultures. Although colony growth depended absolutely on exogenous IL 2 in three cases (ALL), in the three other cases (one ALL, two NHL) some colonies grew also when no IL 2 had been added to the cultures. Upon further analysis of the cells of one of the latter patients, it was found that the cells produced IL 2 and proliferated in response to this endogenous IL 2. The results from this study indicate that the requirements of endogenous v exogenous IL 2 for cell proliferation in T-ALL and T-NHL and IL 2 receptor activation by PHA and TPA vary from patient to patient. In addition, they support the notion that T-ALL and T-NHL cells have not lost dependence on IL 2 and IL 2 receptor activation for in vitro growth.
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000473:pathology*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2