{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:10:46Z","timestamp":1777918246296,"version":"3.51.4"},"reference-count":70,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tumori"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:p>Transforming growth factor beta 1 (TGF-\u03b21) is the prototypic member of a large family of structurally related pleiotropic-secretedcytokines. The TGF-\u03b21\/SMAD signaling pathway usually participates in a wide range of cellular processes such as growth, proliferation, differentiation and apoptosis. Upon binding onTGF-\u03b21, the dimerized TGF-\u03b2 type II receptors recruit and phosphorylate the TGF-\u03b2 type I receptors, which phosphorylate the receptor-regulated SMAD (SMAD2 and SMAD3) presented by the SMAD anchor for receptor activation.<\/jats:p>\n                  <jats:p>The phosphorylated receptor-regulated SMAD form heterologous complexes with the common-mediator SMAD (SMAD4) and subsequently translocate into the nucleus, where they interact with other transcription factors to regulate the expression of target genes. This multi-functional signaling pathway modulated by various elements with complex mechanisms at different levels is also inevitably involved in cancer. We herein present data on the role of the TGF-\u03b21\/SMAD signaling pathway in human chronic myeloid leukemia and explain the potent biological effects of TGF-\u03b21 on leukemia cells. The paper is based on a review of articles selected from Cancerline and Medline data bases.<\/jats:p>\n                  <jats:p>The constitutively active tyrosine kinase produced by the specific Bcr-Abl fusion gene on the Philadelphia chromosome can enhance the resistance of malignant cells to TGF-\u03b21-induced growth inhibition and apoptosis, which contributes to enhancement of proteasomal degradation of p27. However, overexpression of the EVI1 gene, which is also caused by Bcr-Abl, can recruit the C-terminal binding protein and histone deacetylase to prevent the MH2 domain on SMAD3. The later is essential for transcription activation on target genes and leads to blockage of the TGF-\u03b21\/SMAD signaling pathway.<\/jats:p>\n                  <jats:p>Some studies have indicated that certain therapeutic agents applied in clinical treatment can inhibit proliferation and promote differentiation of leukemia cells by way of modulation of the TGF-\u03b21\/SMAD signal pathway. For example, arsenic trioxide can promote specific degradation of the AML1\/MDS1\/EVI1 oncoprotein and inhibit the proliferation of leukemia cells. However, specific histone deacetylase inhibitors can interrupt the effect of histone deacetylase to alleviate EVI1-mediated suppression of TGF-\u03b21\/SMAD signaling. The tyrosine kinase inhibitor in the target therapy of chronic myeloid leukemia can effectively inhibit the tyrosine kinase activity of Bcr-Abl and induce suppression on the TGF-\u03b21\/SMAD signaling pathway.<\/jats:p>\n                  <jats:p>The TGF-\u03b21\/SMAD signaling pathway plays an important role in chronic myeloid leukemia cells and leads the leukemia cells to growth inhibition, differentiation and apoptosis. The positive influence of the TGF-\u03b21\/SMAD signaling pathway in chronic myeloid leukemia is fairly significant, and its potential effects in clinical treatment will bring about definite benefits.<\/jats:p>\n                  <jats:p>Since it is a complex signaling pathway widely involved in many aspects of cellular activities, further study and comprehensive analysis of the TGF-\u03b21\/SMAD signaling pathway are imperative and will have a guiding significance in research and clinical applications. It is an exciting area for future research. Free full text available at www.tumorionline.it<\/jats:p>","DOI":"10.1177\/030089161009600503","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T04:25:46Z","timestamp":1519705546000},"page":"659-666","source":"Crossref","is-referenced-by-count":28,"title":["The Transforming Growth Factor Beta 1\/SMAD Signaling Pathway Involved in Human Chronic Myeloid Leukemia"],"prefix":"10.1177","volume":"96","author":[{"given":"Enyu","family":"Su","sequence":"first","affiliation":[{"name":"Key Laboratory for Modern Medicine and Technology of Shandong Province, Institute of Basic Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guosheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Modern Medicine and Technology of Shandong Province, Institute of Basic Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,1,29]]},"reference":[{"key":"bibr1-030089161009600503","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.753"},{"key":"bibr2-030089161009600503","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1189\/jlb.71.5.731","volume":"71","author":"Sylviance D.","year":"2002","journal-title":"J Leukocyte Biol"},{"key":"bibr3-030089161009600503","first-page":"2068","volume":"46","author":"Shipley G.D.","year":"1986","journal-title":"Cancer 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