Molecular genetics in chronic B cell lymphoproliferative disorders
Research type
Research Study
Full title
Molecular genetics in chronic B cell lymphoproliferative disorders
IRAS ID
177038
Contact name
H Denis Alexander
Contact email
Sponsor organisation
Professor
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Rationale: Patients with B cell chronic lymphoproliferative disorders (B CLPD), are increasingly recognised as having several sub-clones of tumour cells, all defined by the same immunoglobulin (antibody) production (hence traditionally thought of as monoclonal) but likely to have different characteristics contributing to drug resistance and death signal evasion.
Hypothesis: That relapse in B CLPD is likely to result from the presence of a ‘more malignant’ or ‘drug resistant’ sub-clone following treatment, presently undetected using conventional criteria to define response. Separation and scrutiny of these residual cells should yield important information on the mechanisms of death evasion and therapeutic drug resistance, which should complement cell line work presently underway.
Samples: BM aspirate and/or PB samples will be requested from patients at normal sampling times, including: presentation, completion of initial treatment, relapse and/or when drug resistance develops.
Methods: Eight (or more) colour flow cytometric method(s) are being developed. Hierarchal (sequential) gating will allow identification and capture of residual tumour cells, using the powerful in house cell separator (FACSAria). Investigations, including cytogenetic and molecular genetic studies will be undertaken to study mechanisms of drug resistance and death evasion pathways.Projected outcome(s): This approach should yield: 1)valuable clinical information on the presence of residual tumour cells (MRD) at various stages in the disease pathway, with a sensitivity considerably higher than that provided by conventional methods; 2) establish whether the inevitable relapse seen in most patients is due to residual tumour currently undetected following treatment; 3) cellular and molecular scrutiny of residual tumour cells separated using the FACSAria should lead to an enhanced understanding of the biology of B-CLPD, including multiple myeloma, and identify key events contributing to disease progression and development of drug resistance. This will complement the multiple myeloma cell line work currently underway in Derry, Boston and Dublin.
REC name
HSC REC B
REC reference
15/NI/0095
Date of REC Opinion
15 Jul 2015
REC opinion
Further Information Favourable Opinion