Transcriptional and niche dysregulation in CMML
Research type
Research Study
Full title
Investigating the role of transcriptional and microenvironmental dysregulation in Chronic Myelomonocytic Leukaemia
IRAS ID
241557
Contact name
Kiran Batta
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
Chronic myelomonocytic leukaemia (CMML) is a rare blood cell disease characterized by non-functional monocytes. The median age at CMML diagnosis is 65-70 years. Nearly all CMML cases are unmanageable to standard therapies and this is mainly due to the poor understanding of the basic mechanisms that drive disease progression. Nearly all CMML patients carry gene mutations in a group of genes called epigenetic factors and splicing factors. It is not known how mutations in these factors cause CMML. Our project will investigate from various angles how mutations in these factors cause CMML. This will include detailed analyses of the transcriptome i.e. gene expression, splicing abnormalities, DNA modification changes, and genomic landscape in patients and healthy controls. We will investigate how these changes translate into the protein landscape of CMML cells. We will use CMML patient samples direct from the clinic and cryopreserved in the Manchester Cancer Research Centre Tissue Biobank (approvals for this already in place). This IRAS application is mainly to access a source of normal/healthy blood monocytes, blood stem cells and mesenchymal stem cells to serve as necessary experimental controls. Since CMML is commonly seen in elderly individuals, we aim to obtain these control samples from healthy individuals over 60 years old. Monocytes will be isolated from leukocyte cone filters supplied by the NHS Blood and Transplant Service as a by-product of blood donation or from healthy volunteers within the research institute. Bone marrow will be isolated from discarded tissue material from patients undergoing hip replacement surgery. The study will be conducted in the research laboratories at Manchester Cancer Research Centre. Together, the information from our project will reveal novel insights into CMML biology and facilitate development of novel therapeutic strategies for this under-researched disease with poor patient outcomes.
REC name
London - Harrow Research Ethics Committee
REC reference
19/LO/0564
Date of REC Opinion
2 Apr 2019
REC opinion
Further Information Favourable Opinion