{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T22:15:10Z","timestamp":1776464110154,"version":"3.51.2"},"reference-count":29,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>P57KIP2 is a cyclin-dependent kinase inhibitor silenced in a variety of human malignancies. DNA methylation of a region surrounding the transcription start site of p57KIP2 was found in acute lymphocytic leukemia (ALL)\u2013derived cell lines. Methylation of this region correlated with gene silencing, and treatment of methylated\/silenced cell lines with 5-aza-2\u2032-deoxycytidine resulted in gene re-expression. P57KIP2 was methylated in 31 (50%) of 63 patients with newly diagnosed ALL, and in 11 (52%) of 21 patients with relapsed ALL. In 5 of them (25%), methylation was acquired at relapse. No association was observed between methylation of p57KIP2 alone and clinical-biologic characteristics studied, including overall survival (OS) or disease-free survival. Methylation of multiple genes in a cell-cycle regulatory pathway composed of p73, p15, and p57KIP2 occurred in 22% of Philadelphia chromosome (Ph)\u2013negative patients. Ph-negative patients with methylation of 2 or 3 genes of this pathway had a significantly worse median OS compared with those with methylation of 0 or 1 gene (50 vs 467 weeks, respectively;P\u2009=\u2009.02). Our results indicate that p57KIP2 is frequently methylated in adult patients with ALL, and that inactivation of a pathway composed of p73, p15, and p57KIP2 predicts for poor prognosis in Ph-negative patients.<\/jats:p>","DOI":"10.1182\/blood-2002-08-2466","type":"journal-article","created":{"date-parts":[[2003,5,5]],"date-time":"2003-05-05T19:24:00Z","timestamp":1052162640000},"page":"4131-4136","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":111,"title":["Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia"],"prefix":"10.1182","volume":"101","author":[{"given":"LanLan","family":"Shen","sequence":"first","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Toyota","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Kondo","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiro","family":"Obata","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Daniel","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry","family":"Pierce","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohzoh","family":"Imai","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagop M.","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre J.","family":"Issa","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Garcia-Manero","sequence":"additional","affiliation":[{"name":"From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111703275771300_B1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrg816","article-title":"The fundamental role of epigenetic events in cancer.","volume":"3","author":"Jones","year":"2002","journal-title":"Nat Rev 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