10648600

pubmed:Citation

4

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of a hematopoietic stem cell. The majority of cases of CML are associated with the (9;22) chromosome translocation that generates the bcr-abl chimeric gene. Alpha interferon (IFN-alpha) treatment induces hematological remission and prolongs life in 75% of CML patients in the chronic phase. It has been shown that mice deficient in interferon consensus sequence binding protein (ICSBP), a member of the interferon regulatory factor family, manifest a CML-like syndrome. We have shown that expression of Bcr-Abl in bone marrow (BM) cells from 5-fluorouracil (5-FU)-treated mice by retroviral transduction efficiently induces a myeloproliferative disease in mice resembling human CML. To directly test whether icsbp can function as a tumor suppressor gene, we examined the effect of ICSBP on Bcr-Abl-induced CML-like disease using this murine model for CML. We found that expression of the ICSBP protein was significantly decreased in Bcr-Abl-induced CML-like disease. Forced coexpression of ICSBP inhibited the Bcr-Abl-induced colony formation of BM cells from 5-FU-treated mice in vitro and Bcr-Abl-induced CML-like disease in vivo. Interestingly, coexpression of ICSBP and Bcr-Abl induced a transient B-lymphoproliferative disorder in the murine model of Bcr-Abl-induced CML-like disease. Overexpression of ICSBP consistently promotes rather than inhibits Bcr-Abl-induced B lymphoproliferation in a murine model where BM cells from non-5-FU-treated donors were used, indicating that ICSBP has a specific antitumor activity toward myeloid neoplasms. We also found that overexpression of ICSBP negatively regulated normal hematopoiesis. These data provide direct evidence that ICSBP can act as a tumor suppressor that regulates normal and neoplastic proliferation of hematopoietic cells.

http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-10224280, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-10490629, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-1460054, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-1691092, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-1730873, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-178822, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-2111015, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-2179728, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-2204061, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-2406902, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-3047582, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-4318922, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7518835, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7526889, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7537982, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7678054, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7690960, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7797077, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7926767, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-7992097, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8133040, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8197182, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8479746, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8541551, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8621906, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8839828, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8861914, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8951783, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-8958917, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9028327, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9092512, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9348310, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9348311, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9414265, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9474745, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9490692, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9593745, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9635566, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9808572, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9808576, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9865486, http://linkedlifedata.com/resource/pubmed/commentcorrection/10648600-9916702

http://linkedlifedata.com/resource/pubmed/journal/8109087

http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic, http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers, http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil, http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors, http://linkedlifedata.com/resource/pubmed/chemical/Interferons, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-8

Feb

pubmed-author:RAOK RKR, pubmed-author:ReaGG

20

Y

2009-11-18