IMPAIRED PROLIFERATION AND DIFFERENTIATION OF MYELODYSPLASTIC CD34+ CELLS

被引:12
作者
SAWADA, K
机构
[1] Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo
关键词
MDS; CD34; PURIFICATION; SERUM-FREE MEDIUM; G-CSF;
D O I
10.3109/10428199409049649
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of hematopoiesis entailing hyperproliferative and ineffective hematopoiesis resulting in refractory cytopenia(s), and increased risk of transformation into acute myeloblastic leukemia (AML). The widely used classification defined by the French-American-British group (FAB) recognizes 5 cytological subtypes of different prognosis, based essentially on the presence and the frequency of marrow blasts. The percentage of marrow blasts does not exceed 30%, hence, direct investigations of biological and biochemical events of MDS blast cells have been hampered. The CD34 antigen is currently unique in its narrow specificity of expression on human lymphohematopoietic progenitor cells. This cell membrane phosphoglycoprotein has been used for immunologic blast cell purification, notwithstanding the frequency of marrow blasts, and has provided a set of tools for investigations of MDS i.e. a direct comparison of the nature of blast cells in each of the MDS subtypes, using immunologic, biologic, biochemical and molecular biological methodology. A combination of serum-free medium and a purification method for blast cells provided evidence that the progenitor eel growth abnormalities in these disorders involve a defect in the capacity of progenitor cells to respond to stimulation with growth factor(s), and has presented direct evidence for the manner in which myelodysplastic CD34(+) cells are impaired.
引用
收藏
页码:37 / 47
页数:11
相关论文
共 116 条
  • [41] San Miguel J.F., Gonzalez M., Canizo M.C., Anta J.P., Hernandez J., Ortega F., Lopez Borrasca A., The nature of blast cells in myelodysplastic syndromes evolving to acute leukaemia, Blut, 52, pp. 357-363, (1986)
  • [42] Guyotat D., Campos L., Thomas X., Vila L., Shi Z.-H., Charrin C., Gentilhomme O., Fiere D., Myelodysplastic syndromes: A study of surface markers and in vitro growth patterns, Am. J. Hematol., 34, pp. 26-31, (1990)
  • [43] Katz F., Tindle R., Sutherland R., Greaves M.F., Identification of a membrane glycoprotein associated with haematopoietic progenitor cells, Leukemia Res., 9, pp. 191-198, (1985)
  • [44] Andrew R.G., Singer J.W., Bernstein I.D., Monoclonal antibody 12–8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors, Blood, 67, pp. 842-845, (1986)
  • [45] Watt S.M., Karhi K., Gatter K., Furley A.J.W., Katz F.E., Healy L.E., Attass L.J., Bradley N.J., Sutherland D.R., Levinsky R., Greaves M.F., Distribution and epitope analysis of the cell membrane glycoprotein (HPCA-1) associated with human hemopoietic progenitor cells, Leukemia, 1, pp. 417-426, (1987)
  • [46] Sutherland D.R., Watt S.M., Dowden G., Karhi K., Baker M.A., Greaves M.F., Smart J.E., Structural and partial amino acid sequence analysis of the human hemopoietic progenitor antigen CD34, Leukemia, 2, pp. 793-803, (1989)
  • [47] Molgaard H.V., Spurr N.K., Greaves M.F., The hemopoietic stem cell antigen, CD34, is encoded by a gene located on chromosome 1, Leukemia, 3, pp. 773-776, (1989)
  • [48] Fackler M.J., Civin C.I., Sutherland D.R., Baker M.A., May W.S., Activated protein kinase C directly phosphorylates the CD34 antigen on hematopoietic cells, J. Biologic. Chem., 265, pp. 11056-11061, (1990)
  • [49] Fackler M.J., Civin C.I., May W.S., Upregulation of surface CD34 is associated with protein kinase C-mediatcd hyperphosphorylation of CD34, J. Biolog. Chem., 267, pp. 17540-17546, (1992)
  • [50] Sutherland D.R., Fackler M.J., May W.S., Matthews K.E., Baker M.A., Activated protein kinase C directly phosphorylates the CD34 antigen in acute lymphoblastic leukemia cells, Leukemia & Lymphoma, 8, pp. 337-344, (1992)