Structure/function analyses of IL-2 binding proteins on human B cell precursor acute lymphoblastic leukemias.
We have studied the expression and function of interleukin-2 (IL-2) receptors on B cell precursor acute lymphoblastic leukemias (ALL). After incubation of B cell precursor ALL in vitro for 24 hr, 11 out of 17 leukemic bone marrow aspirates expressed the Tac/CD25 protein (greater than 10% positive blasts). Expression of Tac/CD25 on the leukemic cells was confirmed by two color flow cytometric analysis using anti-Tac/CD25 and anti-CALLA/CD10 monoclonal antibodies. The molecular mass of the B cell precursor ALL Tac/CD25 protein was 55 kilodaltons (kD), identical to that on activated T cells. Binding of radiolabeled IL-2 in two leukemic bone marrow aspirates demonstrated the presence of high affinity IL-2 receptors. Cross-linking of 125I-labeled IL-2 to TPA activated B cell precursor ALL revealed the 55 kD Tac/CD25 protein and an additional protein of 75 kD. Recombinant IL-2 in concentrations of 10-1,000 U/ml had essentially no proliferative effect in 10 patients tested, whereas low molecular weight B cell growth factor (L-BCGF) induced proliferation in 8 of 10 patients. L-BCGF also induced expression of CD20 in 3 of 7 CD20 negative B cell precursor ALL. IL-2 did not induce CD20, but enhanced its expression in the 3 patients who responded to L-BCGF. We conclude that IL-2 has essentially no proliferative effect on B cell precursor ALL, despite the presence of high affinity IL-2 receptors and the presence of the IL-2 binding cell surface molecules similar to those on activated T cells. IL-2 may, however, induce a phenotypic change (CD20 acquisition) consonant with differentiation in synergy with L-BCGF.
D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D007945:Leukemia, Lymphoid / Q000473:pathology*; D011971:Receptors, Immunologic / Q000032:analysis*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins