{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:11:03Z","timestamp":1790244663592,"version":"4.1.0"},"reference-count":15,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,7,15]]},"abstract":"<jats:p>In myelodysplastic syndrome (MDS), the expression of the cyclin-dependent kinase inhibitor p15ink4B (p15) is frequently decreased because of the aberrant methylation of the gene promoter; p15 is normally up-regulated during megakaryocytic differentiation. It was hypothesized that p15 methylation and deregulation of gene expression contribute to defective megakaryocytopoiesis in patients with MDS. Here it is shown that the increasing autocrine production of TGF-\u03b21 stimulates megakaryocytic differentiation in normal CD34+ cells and that p15 mediates, at least in part, this effect. This TGF-\u03b21\u2013dependent pathway is altered in MDS CD34+progenitors because of p15 methylation. The demethylating agent 2-deoxyAZAcytidin can restore the normal demethylated state of thep15 gene and increase its expression. Nevertheless, MDS CD34+ cells only poorly differentiate to the megakaryocytic lineage. These findings suggest that p15 methylation occurs in a neoplastic clone with a profound defect of cell proliferation, survival, and differentiation that cannot be overcome by using a demethylating drug.<\/jats:p>","DOI":"10.1182\/blood.v98.2.495","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"495-497","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["Expression of p15ink4b gene during megakaryocytic differentiation of normal and myelodysplastic hematopoietic progenitors"],"prefix":"10.1182","volume":"98","author":[{"given":"Luciana","family":"Teofili","sequence":"first","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Martini","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Di Mario","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Rutella","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Urbano","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Luongo","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Leone","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Maria","family":"Larocca","sequence":"additional","affiliation":[{"name":"From the Institutes of Hematology and Pathology, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221413360900_B1","first-page":"1133","article-title":"Expression of p15INK4B in normal 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