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Accession Number ADA567467
Title Regulation and Function of TIFAB in Myelodysplastic Syndrome.
Publication Date Jun 2012
Media Count 24p
Personal Author D. Starczynowski
Abstract Myelodysplastic syndromes (MDS) are clonal bone marrow failure (BMF) disorders defined by blood cytopenias due to ineffective hematopoiesis, genomic instability, and a predisposition to acute myeloid leukemia (AML). The most commonly recurring genomic alteration in MDS is deletion of chromosome 5q (del(5q)). MDS patients with an isolated del(5q) presenting with anemia, neutropenia, and elevated platelets associated with dysplastic megakaryocytes are considered to have 5q- syndrome. The majority of MDS patients with del(5q) do not exhibit these particular symptoms and, instead, are referred to as del(5q) MDS . We have recently identified miR-146a, which target the TRAF6 arm of the innate immune pathway, a gene within the deleted region in del(5q) MDS. We posit that multiple genes on chr 5q coordinate TRAF6 activation in del(5q) MDS. A search of annotated genes within or near the CDRs revealed a known inhibitor of TRAF6, TIFAB, on band q31.1. We hypothesize that deletion of TIFAB promotes activation of the TRAF6 complex in human CD34+ cells resulting in hematopoietic defects resembling MDS and AML with del(5q). The overall objectives of this proposal are to (1) determine whether loss of TIFAB in human CD34+ cells contributes to MDS in mice; (2) to investigate whether deletions of TIFAB and miR-146a cooperate to activate TRAF6 in MDS; and (3) to determine the consequences of TIFAB deletion on signal transduction in human CD34+ cells, and whether these could explain features of MDS. In preliminary data from the first year of the proposal, we have evidence that TIFAB exhibits tumor suppressor- like functions in human hematopoietic cells.
Keywords Blood platelets
Bone marrow
Hematopoietic system
Myelodysplastic syndromes
Signs and symptoms

Source Agency Non Paid ADAS
NTIS Subject Category 57A - Anatomy
57S - Physiology
57E - Clinical Medicine
Corporate Author Children's Hospital Medical Center, Cincinnati, OH.
Document Type Technical report
Title Note Annual rept. 1 Jun 2011-30 May 2012.
NTIS Issue Number 1309
Contract Number W81XWH-11-1-0468

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