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Expression of thrombopoietin and its receptor (c‐mpl) in chronic myelogenous leukemia
Author(s) -
Kaban Kerim,
Kantarjian Hagop,
Talpaz Moshe,
O'Brien Susan,
Cortes Jorge,
Giles Francis J.,
Pierce Sherry,
Albitar Maher
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000201)88:3<570::aid-cncr12>3.0.co;2-i
Subject(s) - thrombopoietin , medicine , chronic myelogenous leukemia , thrombopoietin receptor , bone marrow , haematopoiesis , immunology , progenitor cell , leukemia , hematology , interferon , philadelphia chromosome , cancer research , stem cell , biology , chromosomal translocation , biochemistry , genetics , gene
BACKGROUND Chronic myelogenous leukemia (CML) represents a paradigm of the stepwise increment in disease aggressiveness, resistance to therapy, and transformation. Thrombopoietin (TPO) and its receptor, c‐mpl, support the proliferation of multiple types of immature hematopoietic progenitor cells, and induce clonal growth of leukemic cells. The authors investigated whether TPO or c‐mpl overexpression might correlate with progression of CML, disease aggressiveness, or response to therapy. METHODS Expression of c‐mpl and TPO was measured in bone marrow samples from 208 patients with CML by Western blot analysis and solid‐phase plate radioimmunoassay (used for quantification). Samples obtained from individuals without evidence of hematologic abnormalities were used as controls. RESULTS There were no significant differences in TPO or c‐mpl expression among patients in different phases of CML or between patients with Philadelphia chromosome positive and negative CML. When TPO and c‐mpl levels were analyzed in relation to prognostically important host and disease characteristics in early chronic phase CML, platelet and white blood cell counts demonstrated significant differences in both TPO and c‐mpl expression, but age and spleen size demonstrated significant differences in TPO expression only. Responses to interferon (INF)‐α‐based therapy and survival were not influenced by TPO or c‐mpl levels. CONCLUSIONS TPO or c‐mpl overexpression did not correlate with different CML phases, suggesting that they were not involved in CML progression from early to advanced phase. Neither TPO nor c‐mpl overexpression was particularly evident in any risk group, suggesting lack of correlation between their expression and disease aggressiveness. This was supported by the finding of similar response to IFN‐α‐based therapy and survival regardless of the level of TPO or c‐mpl expression. Cancer 2000;88:570–6. © 2000 American Cancer Society.