{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:51:31Z","timestamp":1764996691487},"reference-count":23,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>p15INK4b and p16INK4a proteins are cell cycle regulators involved in the inhibition of G1 phase progression. High frequency of methylation of both genes has been reported in multiple myeloma (MM), but it remains to be determined how and when these alterations contribute to tumorigenesis. Monoclonal gammopathy of undetermined significance (MGUS) represents an early disease stage in a fraction of MMs. Plasma cells from 33 patients with MGUS and 33 patients with MM were isolated and analyzed forp15INK4b and p16INK4amethylation by methylation-specific polymerase chain reaction. Selective methylation was found in 19% forp16INK4a, 36% forp15INK4b, and 6.5% for both genes in MGUS, and frequencies were similar in MM suggesting that methylation of these genes is an early event, not associated with transition from MGUS to MM. p15INK4b andp16INK4a gene methylation might contribute to immortalization of plasma cells rather than malignant transformation in the natural history of MM.<\/jats:p>","DOI":"10.1182\/blood.v98.1.244","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T08:46:47Z","timestamp":1027759607000},"page":"244-246","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":65,"title":["p16\n          \n            INK4a\n           andp15INK4b gene methylations in plasma cells from monoclonal gammopathy of undetermined significance"],"prefix":"10.1182","volume":"98","author":[{"given":"Gae\u0308lle","family":"Guillerm","sequence":"first","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Gyan","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darius","family":"Wolowiec","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Facon","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herve\u0301","family":"Avet-Loiseau","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazimierz","family":"Kuliczkowski","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Bauters","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Fenaux","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Quesnel","sequence":"additional","affiliation":[{"name":"From the Unite\u0301 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France; the Department of Hematology, Wroclaw Medical University, Wroclaw, Poland; and the Laboratoire d'He\u0301matologie, CHU Nantes, Nantes, France."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021220564619100_B1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S0025-6196(12)60015-9","article-title":"\u201cBenign\u201d monoclonal gammopathy\u2014after 20 to 35 years of follow-up.","volume":"68","author":"Kyle","year":"1993","journal-title":"Mayo Clin Proc."},{"key":"2020021220564619100_B2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1200\/JCO.1994.12.8.1577","article-title":"Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945.","volume":"12","author":"Kyle","year":"1994","journal-title":"J Clin Oncol."},{"key":"2020021220564619100_B3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1182\/blood.V91.1.3","article-title":"Multiple myeloma: increasing evidence for a multistep transformation process.","volume":"91","author":"Hallek","year":"1998","journal-title":"Blood."},{"key":"2020021220564619100_B4","first-page":"168","article-title":"Transcriptional silencing of the p16 gene in human myeloma-derived cell lines by hypermethylation.","volume":"103","author":"Wong","year":"1998","journal-title":"Br J Haematol."},{"key":"2020021220564619100_B5","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1046\/j.1365-2141.1998.00724.x","article-title":"Methylation of the p16INK4A gene in multiple myeloma.","volume":"101","author":"Tasaka","year":"1998","journal-title":"Br J Haematol."},{"key":"2020021220564619100_B6","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1046\/j.1365-2141.1997.8552482.x","article-title":"Analysis of the p16INK4A, p15INK4B and p18INK4C genes in multiple myeloma.","volume":"96","author":"Tasaka","year":"1997","journal-title":"Br J Haematol."},{"key":"2020021220564619100_B7","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1038\/sj.leu.2401557","article-title":"Expression of p16INK4A and p14ARF in hematological malignancies.","volume":"13","author":"Taniguchi","year":"1999","journal-title":"Leukemia."},{"key":"2020021220564619100_B8","first-page":"2173","article-title":"Characterization of p16(INK4A) expression in multiple myeloma and plasma cell leukemia.","volume":"3","author":"Urashima","year":"1997","journal-title":"Clin Cancer Res."},{"key":"2020021220564619100_B9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/sj.leu.2401617","article-title":"De novo methylation of tumor suppressor gene p16\/INK4a is a frequent finding in multiple myeloma patients at diagnosis.","volume":"14","author":"Gonzalez","year":"2000","journal-title":"Leukemia."},{"key":"2020021220564619100_B10","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1182\/blood.V89.7.2500","article-title":"Frequent hypermethylation of p16 and p15 genes in multiple myeloma.","volume":"89","author":"Ng","year":"1997","journal-title":"Blood."},{"key":"2020021220564619100_B11","first-page":"1655","article-title":"Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients: implications for the differential diagnosis between MGUS and multiple myeloma.","volume":"152","author":"Ocqueteau","year":"1998","journal-title":"Am J Pathol."},{"key":"2020021220564619100_B12","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1182\/blood.V90.9.3682","article-title":"Several cytogenetic subclones may be identified within plasma cells from patients with monoclonal gammopathy of undetermined significance, both at diagnosis and during the indolent course of this condition.","volume":"90","author":"Zandecki","year":"1997","journal-title":"Blood."},{"key":"2020021220564619100_B13","doi-asserted-by":"crossref","first-page":"9821","DOI":"10.1073\/pnas.93.18.9821","article-title":"Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.","volume":"93","author":"Herman","year":"1996","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021220564619100_B14","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1182\/blood.V91.8.2985.2985_2985_2990","article-title":"Methylation of the p15(INK4b) gene in myelodysplastic syndromes is frequent and acquired during disease progression.","volume":"91","author":"Quesnel","year":"1998","journal-title":"Blood."},{"key":"2020021220564619100_B15","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1182\/blood.V94.8.2583.420a05_2583_2589","article-title":"Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma. 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