Title |
The role of ETV6 in T-cell acute lymphoblastic leukemia
|
Institution |
COLUMBIA UNIVERSITY HEALTH SCIENCES, NEW YORK, NY
|
Principal Investigator |
FERRANDO, ADOLFO
|
NCI Program Director |
McCarthy
|
Cancer Activity |
Immunology
|
Division |
DCB
|
Funded Amount |
$322,040
|
Project Dates |
02/01/2013 - 01/31/2018
|
Fiscal Year |
2014
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
Childhood Cancers (50.0%)
|
Childhood Leukemia (50.0%)
Leukemia (100.0%)
|
Research Type |
Cancer Initiation: Alterations in Chromosomes
Cancer Initiation: Oncogenes and Tumor Suppressor Genes
|
Abstract |
DESCRIPTION (provided by applicant): This project aims to establish the oncogenic mechanisms activated by ETV6 mutations in T- cell acute lymphoblastic leukemia (T-ALL). Our central hypothesis is that ETV6 mutations found in T- ALL result in expression of dominant negative ETV6 isoforms whose expression disrupts specific transcriptional regulatory networks that control cell proliferation, differentiation and survival in T-cell progenitor cells. In additin, we propose that ETV6 mutations cooperate with activating mutations in loss of function mutations and deletions in EZH2 in T-ALL. Thus, the goals of this research proposal are to define the transcriptional programs and oncogenic pathways responsible for the pathogenesis of mutant ETV6 induced T-ALL. To achieve these objectives we propose: (i) to define the transcriptional program controlled by mutant ETV6 in T-ALL; and (iii) to analyze the genetics of mutant ETV6 induced transformation using a mouse models of mutant ETV6 induced T-ALL. |