19958752

Source:http://linkedlifedata.com/resource/pubmed/id/19958752

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0010802, umls-concept:C0314603, umls-concept:C1336735, umls-concept:C1704259, umls-concept:C1705987
pubmed:issue	1-2
pubmed:dateCreated	2010-3-26
pubmed:abstractText	Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML) are late complications of cytotoxic therapy used in the treatment of malignant diseases. The most common subtype of t-AML ( approximately 75% of cases) develops after exposure to alkylating agents, and is characterized by loss or deletion of chromosome 5 and/or 7 [-5/del(5q), -7/del(7q)], and a poor outcome (median survival 8 months). In the University of Chicago's series of 386 patients with t-MDS/t-AML, 79 (20%) patients had abnormalities of chromosome 5, 95 (25%) patients had abnormalities of chromosome 7, and 85 (22%) patients had abnormalities of both chromosomes 5 and 7. t-MDS/t-AML with a -5/del(5q) is associated with a complex karyotype, characterized by trisomy 8, as well as loss of 12p, 13q, 16q22, 17p (TP53 locus), chromosome 18, and 20q. In addition, this subtype of t-AML is characterized by a unique expression profile (higher expression of genes) involved in cell cycle control (CCNA2, CCNE2, CDC2), checkpoints (BUB1), or growth (MYC), loss of expression of IRF8, and overexpression of FHL2. Haploinsufficiency of the RPS14, EGR1, APC, NPM1, and CTNNA1 genes on 5q has been implicated in the pathogenesis of MDS/AML. In previous studies, we determined that Egr1 acts by haploinsufficiency and cooperates with mutations induced by alkylating agents to induce myeloid leukemias in the mouse. To identify mutations that cooperate with Egr1 haploinsufficiency, we used retroviral insertional mutagenesis. To date, we have identified two common integration sites involving genes encoding transcription factors that play a critical role in hematopoiesis (Evi1 and Gfi1b loci). Of note is that the EVI1 transcription factor gene is deregulated in human AMLs, particularly those with -7, and abnormalities of 3q. Identifying the genetic pathways leading to t-AML will provide new insights into the underlying biology of this disease, and may facilitate the identification of new therapeutic targets.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/CA14599, http://linkedlifedata.com/resource/pubmed/grant/CA40046
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/0227276
pubmed:citationSubset	IM
pubmed:status	MEDLINE
pubmed:month	Mar
pubmed:issn	1872-7786
pubmed:author	pubmed-author:JoslinJohn MJM, pubmed-author:LarsonRichard ARA, pubmed-author:Le BeauMichelle MMM, pubmed-author:QianZhijianZ, pubmed-author:ReshmiShalini CSC, pubmed-author:StoddartAngelaA, pubmed-author:TennantThelma RTR, pubmed-author:YoungDavid JDJ
pubmed:copyrightInfo	Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType	Electronic
pubmed:day	19
pubmed:volume	184
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	50-7
pubmed:meshHeading	pubmed-meshheading:19958752-Animals, pubmed-meshheading:19958752-Cytogenetic Analysis, pubmed-meshheading:19958752-Gene Expression Regulation, Leukemic, pubmed-meshheading:19958752-Humans, pubmed-meshheading:19958752-Leukemia, Myeloid, Acute, pubmed-meshheading:19958752-Neoplasms, Second Primary
pubmed:year	2010
pubmed:articleTitle	Cytogenetic and genetic pathways in therapy-related acute myeloid leukemia.
pubmed:affiliation	Section of Hematology/Oncology, Department of Medicine and the Cancer Research Center, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA.
pubmed:publicationType	Journal Article, Review, Research Support, N.I.H., Extramural