{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:35:42Z","timestamp":1790303742825,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,8,11]],"date-time":"2004-08-11T00:00:00Z","timestamp":1092182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human <jats:italic>L3MBTL<\/jats:italic> gene is located in 20q12, a region that is commonly deleted in myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). <jats:italic>L3MBTL<\/jats:italic> is highly homologous to the D\u2010lethal(3) malignant brain tumor [<jats:italic>D\u2010l(3)mbt<\/jats:italic>] gene, which is a putative tumor\u2010suppressor gene (TSG) identified in <jats:italic>Drosophila<\/jats:italic> and which is closely related to the <jats:italic>Drosophila<\/jats:italic> sex combs on midleg (SCM) protein, a member of the Polycomb group (PcG) family of transcriptional repressors. To examine whether <jats:italic>L3MBTL<\/jats:italic> functions as a \u201cclassic\u201d TSG in human hematologic malignancies, we screened a panel of 17 myeloid leukemia cell lines and peripheral blood or bone marrow samples from 29 MDS and 13 MPD patients for mutations in the entire <jats:italic>L3MBTL<\/jats:italic> coding sequence, including intron\/exon splice junctions. No mutations were identified, although two single nucleotide differences were found (in intron 14 and in exon 15), which were interpreted as polymorphic changes. We used real\u2010time RT\u2010PCR to quantify the level of <jats:italic>L3MBTL<\/jats:italic> mRNA in various normal myeloid and lymphoid cell populations. <jats:italic>L3MBTL<\/jats:italic> is expressed in normal CD34+ bone marrow cells, and we found that the pattern of <jats:italic>L3MBTL<\/jats:italic> expression was similar to that of <jats:italic>BMI<\/jats:italic><jats:italic>1<\/jats:italic>, a well\u2010studied PcG gene with oncogenic activity, suggesting that <jats:italic>L3MBTL<\/jats:italic> and <jats:italic>BMI<\/jats:italic><jats:italic>1<\/jats:italic> may be co\u2010regulated during hematopoiesis. The expression of <jats:italic>L3MBTL<\/jats:italic> mRNA in 30 of 35 cell lines and 13 of 15 AML samples was comparable to the level of <jats:italic>L3MBTL<\/jats:italic> expression in the normal cell populations. However, five leukemia cell lines showed no <jats:italic>L3MBTL<\/jats:italic> expression, and two of the AML samples showed aberrant <jats:italic>L3MBTL<\/jats:italic> expression. These data suggest that <jats:italic>L3MBTL<\/jats:italic> is not mutated in MDS or MPD. However, given the known dosage effects of PcG proteins in regulating gene expression, reduced or absent <jats:italic>L3MBTL<\/jats:italic> expression may be relevant in some cases of myeloid leukemia. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20087","type":"journal-article","created":{"date-parts":[[2004,8,11]],"date-time":"2004-08-11T18:05:06Z","timestamp":1092247506000},"page":"203-213","source":"Crossref","is-referenced-by-count":37,"title":["Structural integrity and expression of the <i>L3MBTL<\/i> gene in normal and malignant hematopoietic cells"],"prefix":"10.1002","volume":"41","author":[{"given":"Donal","family":"MacGrogan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagesh","family":"Kalakonda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Scandura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piernicola","family":"Boccuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertil","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Nimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,8,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1242\/dev.128.9.1587","article-title":"Mice doubly deficient for the Polycomb group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression","volume":"128","author":"Akasaka T","year":"2001","journal-title":"Development"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.d01-1896.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204639"},{"key":"e_1_2_7_5_1","first-page":"2409","article-title":"BMI\u20101 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas","volume":"61","author":"Bea S","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203728"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00285-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300592200"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.5.1621"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg542"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205868"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(93)90052-Y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023085825042"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(02)00052-5"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.20.2678"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.29.120195.001445"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1933744100"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/35101031"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202732"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6408(1998)22:1<74::AID-DVG8>3.0.CO;2-4"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.4.1216"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02385"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204540"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00004-5"},{"key":"e_1_2_7_25_1","unstructured":"MitelmanF JohanssonB MertensF.2004. 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