AML blasts variably express interleukin 2 receptor alpha, beta or gamma chains without measurable effects on proliferation, cytokine message expression or surface expression of adhesion molecules upon stimulation with interleukin 2.
Preliminary clinical studies including interleukin 2 (IL-2) in chemotherapy strategies for treatment of acute myeloblastic leukemia (AML) suggest that IL-2 may improve the disease-free survival of the patients. Because of reports showing interleukin 2 receptor expression on AML blasts, it is important to know whether IL-2 may directly influence these leukemic cells. In initial studies using flow cytometry to analyze surface expression of interleukin 2 receptors (IL-2R), we found expression of the IL-2R alpha chain on blast cells in 26% and of the IL-2R beta-chain in 81% of the patients. To confirm these results at the transcriptional level, we studied the expression of RNA of the IL-2R alpha, beta, and gamma chains by RT-PCR in the bone marrow of 38 newly diagnosed patients with AML and in three AML-derived cell lines. RNA of the alpha chain was detectable in 11/38 patients, the beta chain in 10/38 patients and the gamma chain in 30/38 patients with AML. Blast cells obtained from colonies growing in semisolid media expressed mRNA for IL-2R. RNA for all three IL-2R chains was expressed in lines KG1, HEL 92.1.7 and K562. In comparison with unstimulated cell lines, incubation of the three lines with various amounts of IL-2 over 3 and 14 days did not increase their growth or change message expression of IL-2R, IL-10, and TGF-beta and surface expression of the adhesion molecules CD 11, CD 18, CD 29 and CD 54. In conclusion, despite expression of IL-2 receptors, AML blasts do not respond to IL-2 by proliferation, message expression for various cytokine genes and surface expression of cellular adhesion molecules.
Weidmann
E
E
Department of Internal Medicine, J.W. Goethe University, Frankfurt/M, Germany.
Brieger
J
J
Bergmann
L
L
Hoelzer
D
D
Mitrou
P S
PS
D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008969:Molecular Sequence Data; D012334:RNA, Neoplasm / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D016207:Cytokines; D017931:DNA Primers; D007376:Interleukin-2; D012334:RNA, Neoplasm; D015375:Receptors, Interleukin-2