Linked Life Data

19965692

Source:http://linkedlifedata.com/resource/pubmed/id/19965692

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-1-22
pubmed:abstractText
Acute myeloid leukemias (AMLs) result from multiple genetic alterations in hematopoietic stem cells. We describe a novel t(12;18)(p13;q12) involving ETV6 in a patient with AML. The translocation resulted in overexpression of SETBP1 (18q12), located close to the breakpoint. Overexpression of SETBP1 through retroviral insertion has been reported to confer growth advantage in hematopoietic progenitor cells. We show that SETBP1 overexpression protects SET from protease cleavage, increasing the amount of full-length SET protein and leading to the formation of a SETBP1-SET-PP2A complex that results in PP2A inhibition, promoting proliferation of the leukemic cells. The prevalence of SETBP1 overexpression in AML at diagnosis (n = 192) was 27.6% and was associated with unfavorable cytogenetic prognostic group, monosomy 7, and EVI1 overexpression (P < .01). Patients with SETBP1 overexpression had a significantly shorter overall survival, and the prognosis impact was remarkably poor in patients older than 60 years in both overall survival (P = .015) and event-free survival (P = .015). In summary, our data show a novel leukemogenic mechanism through SETBP1 overexpression; moreover, multivariate analysis confirms the negative prognostic impact of SETBP1 overexpression in AML, especially in elderly patients, where it could be used as a predictive factor in any future clinical trials with PP2A activators.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
615-25
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia.
pubmed:affiliation
Division of Oncology, Center for Applied Medical Research, Spain.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't