|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2008-4-21
|
|
pubmed:abstractText |
Inactivation of p15(Ink4b) expression by promoter hypermethylation occurs in up to 80% of acute myeloid leukemia (AML) cases and is particularly common in the FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO translocation in 40% of cases. To establish whether the loss of p15(Ink4b) contributes to AML progression in association with RUNX1-ETO, we have expressed the RUNX1-ETO fusion protein from a retroviral vector in hematopoietic progenitor cells isolated from wild-type, p15(Ink4b) or p16(Ink4a) knockout bone marrow. Analysis of lethally irradiated recipient mice reconstituted with RUNX1-ETO-expressing cells showed that neither p15(Ink4b) or p16(Ink4a) loss significantly accelerated disease progression over the time period of one year post-transplantation. Loss of p15(Ink4b) alone resulted in increased myeloid progenitor cell frequencies in bone marrow by 10-month post-transplant and a 19-fold increase in the frequency of Lin(-)c-Kit(+)Sca-1(+) (LKS) cells that was not associated with expansion of long-term reconstituting HSC. These results strongly suggest that p15(Ink4b) loss must be accompanied by additional oncogenic changes for RUNX1-ETO-associated AML to develop.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10460585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10647931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10652337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10706859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10851069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10861016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10880462,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-10979955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-11283671,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-11463839,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-11526243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-12086889,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-12091906,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-12101243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-12417632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-12417730,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-12560221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-1391946,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-14513284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-14681685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-14747476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-15988004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-16330818,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-16616331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-16741927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-17284535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-17309820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-7632963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-7795214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-8334990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-8338940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-8499624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-8631003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-8710900,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-9041182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-9418879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-9639410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-9819404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18037485-9819405
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0145-2126
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
32
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1101-11
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:18037485-Animals,
pubmed-meshheading:18037485-Base Sequence,
pubmed-meshheading:18037485-Cell Differentiation,
pubmed-meshheading:18037485-Core Binding Factor Alpha 2 Subunit,
pubmed-meshheading:18037485-Cyclin-Dependent Kinase Inhibitor p15,
pubmed-meshheading:18037485-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:18037485-DNA Primers,
pubmed-meshheading:18037485-Leukemia, Myeloid, Acute,
pubmed-meshheading:18037485-Mice,
pubmed-meshheading:18037485-Mice, Inbred C57BL
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia.
|
|
pubmed:affiliation |
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294, United States.
|
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|
