Linked Life Data

16107895

Source:http://linkedlifedata.com/resource/pubmed/id/16107895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-10-25
pubmed:abstractText
The t(10;11)(p13;q14-21) is found in T-ALL and acute myeloid leukemia and fuses CALM (Clathrin-Assembly protein-like Lymphoid-Myeloid leukaemia gene) to AF10. In order to gain insight into the transcriptional consequences of this fusion, microarray-based comparison of CALM-AF10+ vs CALM-AF10- T-ALL was performed. This analysis showed upregulation of HOXA5, HOXA9, HOXA10 and BMI1 in the CALM-AF10+ cases. Microarray results were validated by quantitative RT-PCR on an independent group of T-ALL and compared to mixed lineage leukemia-translocated acute leukemias (MLL-t AL). The overexpression of HOXA genes was associated with overexpression of its cofactor MEIS1 in CALM-AF10+ T-ALL, reaching levels of expression similar to those observed in MLL-t AL. Consequently, CALM-AF10+ T-ALL and MLL-t AL share a specific HOXA overexpression, indicating they activate common oncogenic pathways. In addition, BMI1, located close to AF10 breakpoint, was overexpressed only in CALM-AF10+ T-ALL and not in MLL-t AL. BMI1 controls cellular proliferation through suppression of the tumor suppressors encoded by the CDKN2A locus. This locus, often deleted in T-ALL, was conserved in CALM-AF10+ T-ALL. This suggests that decreased CDKN2A activity, as a result of BMI1 overexpression, contributes to leukemogenesis in CALM-AF10+ T-ALL. We propose to define a HOXA+ leukemia group composed of at least MLL-t, CALM-AF10 and HOXA-t AL, which may benefit from adapted management.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1948-57
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16107895-Adolescent, pubmed-meshheading:16107895-Adult, pubmed-meshheading:16107895-Cell Proliferation, pubmed-meshheading:16107895-Cell Transformation, Neoplastic, pubmed-meshheading:16107895-Child, pubmed-meshheading:16107895-Gene Expression Profiling, pubmed-meshheading:16107895-Homeodomain Proteins, pubmed-meshheading:16107895-Humans, pubmed-meshheading:16107895-Leukemia-Lymphoma, Adult T-Cell, pubmed-meshheading:16107895-Nuclear Proteins, pubmed-meshheading:16107895-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16107895-Oncogene Proteins, Fusion, pubmed-meshheading:16107895-Proto-Oncogene Proteins, pubmed-meshheading:16107895-Repressor Proteins, pubmed-meshheading:16107895-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16107895-Transcription, Genetic, pubmed-meshheading:16107895-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes.
pubmed:affiliation
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't