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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2005-1-26
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pubmed:databankReference |
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pubmed:abstractText |
Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional knockin strategy to bypass the embryonic lethality caused by MLL-CBP expression and to assess the immediate effects of induced MLL-CBP expression on hematopoiesis. Within days of activating MLL-CBP, the fusion protein selectively expanded granulocyte/macrophage progenitors (GMP) and enhanced their self-renewal/proliferation. MLL-CBP altered the gene expression program of GMP, upregulating a subset of genes including Hox a9. Inhibition of Hox a9 expression by RNA interference demonstrated that MLL-CBP required Hox a9 for its enhanced cell expansion. Following exposure to sublethal gamma-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders. These represented the spectrum of therapy-induced acute myelomonocytic leukemia/chronic myelomonocytic leukemia/myelodysplastic/myeloproliferative disorder similar to that seen in humans possessing the t(11;16). This model of MLL-CBP therapy-related myeloproliferative disease demonstrates the selectivity of this MLL fusion for GMP cells and its ability to initiate leukemogenesis in conjunction with cooperating mutations.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15635450-10393173,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15635450-9859997
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0261-4189
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pubmed:author |
pubmed-author:AkashiKoichiK,
pubmed-author:AnastasiadouEmaE,
pubmed-author:ArmstrongScott ASA,
pubmed-author:ErnstPatriciaP,
pubmed-author:FebboPhillip GPG,
pubmed-author:FisherJill KJK,
pubmed-author:GolubTodd RTR,
pubmed-author:HessJay LJL,
pubmed-author:IwasakiHiromiH,
pubmed-author:KoganScott CSC,
pubmed-author:KorsmeyerStanley JSJ,
pubmed-author:KrivtsovAndreiA,
pubmed-author:KutokJeffery LJL,
pubmed-author:ThornerAaron RAR,
pubmed-author:WangJingJ,
pubmed-author:ZinkelSandra SSS
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
368-81
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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