GATA1/BCLXL EXPRESSION IN MDS
Research type
Research Study
Full title
GATA1 AND BCLXL EXPRESSION IN MDS AND THEIR IMPLICATION IN AZACITIDINE THERAPY
IRAS ID
155548
Contact name
CIRO R RINALDI
Contact email
Sponsor organisation
UNITED LINCOLNSHIRE HOSPITALS NHS TRUST, LINCOLNSHIRE CLINICAL RESEARCH FACILITY
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
The myelodysplastic syndromes (MDS) are a group of blood disorders that have the potential to progress to acute leukaemia (cancer of the white blood cells). The overall survival rates for MDS range from 5-7yrs (low risk) to just 4-5 months (high risk).
In recent years prolonged survival for patients in the intermediate/high risk groups has been achieved by treatment with Azacitidine, a hypomethylating agent. The mode of action of Azacitidine is not fully understood but thought to reduce the potential for progression to leukaemia via two mechanisms; regulating genes to enable normal development of blood cells, and directly killing abnormal cells in the bone marrow. However, for reasons unknown only 40-60% of patients respond to this therapy and of those that do many will later relapse. It is therefore essential to identify those patients unlikely to respond to treatment early in order to best direct them to alternative treatment options and/or trials.Biomarkers are specific markers in the blood that can be measured to ascertain responsiveness to treatment, and therefore also suitability. Current research suggests that levels of GATA1 and Bcl-xL proteins in the blood and bone marrow might correlate with the clinical outcome and response to Azacitidine treatment. This correlation could potentially be exploited for use as a biomarker. GATA1 and Bcl-xL are proteins essential for the normal development of particular blood cells. In healthy individuals the levels of these proteins is tightly regulated by a molecular process called methylation. In MDS, this process is increased, leading to abnormally high levels of these proteins being formed.
In our study we will measure levels of GATA1, BcL-xL and their downstream pathways, in bone marrow and peripheral blood of 80 patients affected by MDS with the purpose of monitoring and evaluating any change in level during Azacitidine treatment.
REC name
London - South East Research Ethics Committee
REC reference
15/LO/0201
Date of REC Opinion
26 Jan 2015
REC opinion
Favourable Opinion