Bone Marrow Microenvironment in Myeloproliferative Neoplasms
Research type
Research Study
Full title
Understanding the role of the Osteoclast/Osteoblast axis and Haematopoietic Niche in Myeloproliferative Neoplasms and effect of therapy (including JAK Inhibitor therapy)
IRAS ID
241371
Contact name
Claire Harrison
Contact email
Sponsor organisation
Guy's and St Thomas NHS Foundation trust
Clinicaltrials.gov Identifier
not applicable yet, Not applicable yet
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
This project focuses on the role of the osteoclast/osteoblast axis and bone marrow hematopoietic niche in myeloproliferative neoplasms (MPN) , mainly focusing on Myelofibrosis, and explores the effects of treatments such as JAK inhibitor (JAKi) therapy. Our knowledge concerning the pathophysiology of MPNs has increased in the last decade since the discovery of the central role of deregulated JAK-STAT signalling pathway within these disorders. In this aspect, research has focused on developing more targeted agents such as JAK inhibitors in clinical trials, and the JAKi Ruxolitinib (Novartis Pharmaceuticals, Switzerland) is the only currently licensed drug for MF and is now also approved for Polycythaemia Vera. Although not a curative approach, many patients may benefit greatly from these agents with regards to reductions in symptom burden and splenomegaly.
These agents can have a pleotropic range of effects on both the innate and adaptive immune system and have profound anti-inflammatory effects and we hypothesize that there will be ‘off-target’ effects on the osteoblast-osteoclast niche. Currently, limited information is available concerning the role of both osteoblasts and osteoclasts in the pathophysiology and prognosis of these diseases. Hence, delineation of the interaction, phenotype and functional capacity role of these cells and potential effects of therapies is highly relevant to understanding MPN pathophysiology and management strategies. Given that we have the largest MPN practice in the United Kingdom at Guy’s Hospital, coupled with Professor Agamemnon Grigoriadis world-renowned expertise in bone biology at King’s College London, we are in a prime position to answer these scientific questions. We have detailed the scientific rationale and methodological aspects of this pilot project as well as the estimated cost. By supporting this project, we expect to enhance knowledge concerning the pathophysiology of MPNs and understand how therapies may affect these pivotal components of the haematopoietic environmental niche.REC name
East of Scotland Research Ethics Service REC 2
REC reference
19/ES/0094
Date of REC Opinion
17 Sep 2019
REC opinion
Further Information Favourable Opinion