IL-2 Receptor (IL-2R) Alpha, Beta, and Gamma Chains Expressed on Blasts of Acute Myelocytic Leukemia May Not Be Functional
Preliminary clinical studies including IL-2 in chemotherapeutic strategies for treatment of acute myelocytic leukemia suggest that IL-2 may improve the overall outcome of the patients [1, 2]. To date, the mechanisms of eradication of blast cells are still unclear. Cytotoxic T and NK cells or secondary cytokines released after administration of IL-2 have been discussed to contribute to the elimination of leukemic cells [3–5]. However, it is important to know, whether IL-2 may directly influence AML blasts . In initial sudies, using flow cytometry, we found expression of considerable levels of the IL-2R alpha chain on blast cells in a low proportion of patients with AML. However, the IL-2R beta chain was more frequently expressed ranging from 0% to 98%. To confirm these results on a transcriptional level, we studied the expression of RNA of the IL-2R α, β, and γ chains by RT PCR in the bone marrow of 39 newly diagnosed patients with AML and in three AML derived cell lines. RNA for all three IL-2R chains was expressed in lines KG1, HEL 92.1.7 and K562. Surface expression of the IL-2R β chain was observed in all three lines, but of the α chain only in KG1 cells. In comparison with unstimulated cell lines incubation of the three lines with various amounts of IL-2 over 3 and 14 days did not influence their growth, measured by cell numbers and 3H-thymidin incorporation. RNA for the α chain was detectable in 12/39 patients, of the β chain in 10/39 patients and the γ chain in 29/39 patients with AML. Altogether the data suggest that the IL-2R expressed on AML blast cells may be incomplete and not functional. In future studies, functional properties of IL-2 R on blast cells obtained from newly diagnosed patients with AML will have to be investigated.
KeywordsAcute Myelocytic Leukemia Acute Leukemia Blast Cell Preliminary Clinical Study Human Acute Leukemia Cell
Unable to display preview. Download preview PDF.
- 2.Bergmann L, Heil G, Kolbe K, Lengfelder E, Brücher J, Lohmeyer J, Mitrou PS, Hoelzer D: Interleukin 2 (IL-2) is a feasible consolidation treatment and may prolong second complete remission (CR) of acute myelocytic leukemia. Ann Hematol 67 (1993) A9.Google Scholar
- 5.Foa R, Guarini A, Tos GA, Cardena S, Fierro MT, Meloni T, Tosto S, Mandelli F, Gavosto F: Peripheral blood and bone marrow immunophenotypic and functional modifications induced in acute leukemia treated with interleukin 2: Evidence for in vivo lymphokine-activated killer cell generation. Cancer Res 51 (1991) 964–968.PubMedGoogle Scholar
- 6.Foa R, Carretto P, Fierro MT, Bonferroni M, Cardena S, Guarini A, Lista P, Pegoraro L, Mandello F, Forni G, Gavosto F: Interleukin 2 does not promote the in vitro and in vivo proliferation and growth of human acute leukemia cells of myeloid and lymphoid origin. Brit J Haematol 75 (1990) 34–40.CrossRefGoogle Scholar
- 15.Aliléche A, Plaisance S, Han DS, Jasmin C, Azzarone B: In human melanoma cells interleukin 2 down modulates the surface expression of histocompatibility antigens class I and class II. Proc Am Assoc Cancer Res 33 (1992) 415.Google Scholar
- 20.Jahn B, Bergmann L, Fenchel K, Weidmann E, Schwulera U, Mitrou PS: CD3+CD4+ T cells as effective cells of autologous blast specific cytotoxicity in acute myelocytic leukemia. Ann Hematol 65, suppl. (1992) A122.Google Scholar