GRANULOCYTE-COLONY-STIMULATING FACTOR, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, PIXY-321, STEM-CELL FACTOR, INTERLEUKIN-3, AND INTERLEUKIN-7 - RECEPTOR-BINDING AND EFFECTS ON CLONOGENIC PROLIFERATION IN ACUTE LYMPHOBLASTIC-LEUKEMIA

被引:14
作者
DRACH, D
ESTROV, Z
ZHAO, SR
DRACH, J
CORK, A
COLLINS, D
KANTARJIAN, H
ANDREEFF, M
机构
[1] Department of Hematology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
[2] Department of Clinical Immunology and Biological Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX
[3] Department of Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX
[4] R and D Systems, Minneapolis, MN
关键词
ALL; CYTOKINES; CYTOKINE RECEPTORS;
D O I
10.3109/10428199409114143
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cytokines are frequently used after chemotherapy of leukemias and solid tumors to augment recovery of normal hematopoiesis. White the regulation of normal and leukemic myelopoiesis is well investigated, little is known about effects of cytokines on growth and differentiation of lymphoblastic leukemia. In this study, we investigated the expression of receptors for G-CSF, GM-CSF, SCF, IL-3, and IL-7 on acute lymphoblastic leukemia (ALL) blasts and the effects of these growth factors (GF) on ALL blast colony formation. The binding of fluorescence-tagged cytokines to receptors on ALL blasts was studied by flow-cytometry in 27 cases of ALL (24 precursor B-ALL, 3 T-ALL). Receptor-binding for myeloid-associated GF was observed in the majority of precursor B-ALL (G-CSF = 100%, GM-CSF = 65%, IL-3 = 83%, SCF = 74%), but not in T-ALL. Binding of labelled IL-7 was detected in both precursor B- (92%) and T-ALL (100%). The presence of receptors for SCF in ALL was confirmed by polymerase chain reaction for c-kit mRNA in 19/21 cases tested. Expression of receptors for G-CSF, GM-CSF, IL-3, and SCF was not associated with expression of myeloid antigens, or with specific cytogenetic abnormalities. The effects of these GF on clonogenic cells were tested in the ALL blast colony assay and varied between samples, but all cytokines were able to increase clonogenic growth. The GM-CSF/IL-3 fusion molecule PIXY-321 was most effective in promoting colony growth. In some cases inhibition of colony formation was found. We conclude that ALL blast cells have receptors not only for IL-7, but also for G-CSF, GM-CSF, SCF, and IL-3. ALL precursors can respond to these GF with changes in their clonogenic growth indicating the presence of functional receptors. Results may have implications for therapeutic approaches combining cytokines and chemotherapy.
引用
收藏
页码:79 / 88
页数:10
相关论文
共 52 条
[1]  
Metcalf D., The molecular control of cell division, differentiation commitment and maturation in hematopoietic cells, Nature, 399, pp. 27-30, (1990)
[2]  
Sobol R.E., Mick R., Royston I., Davey F.R., Ellison R.R., Newman R., Cuttner J., Collins J.D., Griffin H., Nelson D.A., Bloomfield C.D., Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia, N. Engl. J. Med., 316, pp. 1111-1117, (1987)
[3]  
Wiersma S.R., Ortega J., Sobel E., Weinberg K.I., Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood, N. Engl. J. Med., 324, pp. 800-808, (1991)
[4]  
Nishii K., Kita K., Miwa H., Kawakami K., Nakase K., Masuya M., Morita N., Omay S.B., Otsuji N., Fuku-moto M., Shirakawa S., C-kit expression in CD7-positive acute lymphoblastic leukemia: close correlation with expression of myeloid-associated antigen CDI3, Leukemia, 6, pp. 662-668, (1992)
[5]  
Umiel T., Pattengale P., Weinberg K.I., Simultaneous expression of IL-7 receptor (IL7R) and c-kit mRNA in myeloid antigen-positive (MY +) B-lineage ALL, Blood, 78, (1991)
[6]  
Shimoda K., Okamura S., Harada N., Ikematsu W., Kondo S., Kawasaki C., Tanaka T., Etou T., Akashi K., Okamura T., Shibuya T., Harada M., Niho Y., Granulocyte colony-stimulating factor receptors on human acute leukemia: biphenotypic leukemic cells possess granulocyte colony-stimulating factor receptors, Cancer Res., 52, pp. 3052-3055, (1992)
[7]  
Gattei V., Attadia V., Marotta G., Zagonei V., Canale V., Pinto A., Human granulocyte-macrophage colony stimulating factor (GM-CSF) supports the clonogenic growth of B-lineage acute lymphoblastic leukemias (ALLs) coexpressing myeloid antigens, Proc. ASCO, II, (1992)
[8]  
Ohyashiki J.H., Ohyashiki K., Miyauchi J., Fulieda H., Tauchi T., Saito M., Nakazawa S., Kimura N., Clark S.C., Toyama K., Immunogenotypes and clonal culture analysis in B-precursor acute lymphoblastic leukemia, Leukemia, 6, pp. 240-245, (1992)
[9]  
Makrynikola V., Kabral A., Bradstock K.F., Effects of recombinant human cytokines on precursor-B acute lymphoblastic cells, Exp. Hematal., 19, pp. 674-679, (1991)
[10]  
Park L.S., Waldron P.E., Friend D., Sassenfeld H.M., Price V., Anderson D., Cosman D., Andrews R.G., Bernstein I.D., Urdal D.L., Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness, Blood, 74, pp. 56-65, (1989)