JAK2 in Myeloproliferative Neoplasms
Research type
Research Study
Full title
Defining and Targeting Myeloproliferative Neoplasms Using Proteomics
IRAS ID
140680
Contact name
Ciaren Graham
Contact email
Sponsor organisation
University of Lincoln
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Myeloproliferative neoplasms (MPN) are clonal stem cell diseases that can progress to acute leukaemia. Around 3,300 people are diagnosed with MPNs in the UK every year. Classical MPNs include the Philadelphia (BCR-ABL) positive chronic myeloid leukaemia (CML) and the BCR-ABL negative MPNs that include polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis (MF). All MPNs lead to premature death, with the patient’s quality of life adversely affected by disease complications. A protein JAK2 is mutated in a large percentage of MPN patients. As this mutation is found in >95% of PV and 50-60% ET and MF patients it provides an attractive target for therapeutic intervention. Current treatments for MPN include cytoreductive therapy such as hydroxyurea or new molecular targeted therapies such as tyrosine kinase inhibitors (TKIs), exemplified by the JAK inhibitor ruxolitinib in the treatment of MF. A number of clinical trials are currently underway to study the effectiveness of JAK inhibitors in both PV and ET. However, these inhibitors have not wholly lived up to their promise; to date no clinical study has shown that JAK2 inhibitors have eradicated the MPN clonal burden or lessened the likelihood of leukaemic transformation. There is a clear need for new and improved therapies in the treatment of MPN, as existing treatments do not effectively target nor eliminate the population of cancer cells in the haemapoietic niche. These cells are able to self-renew resulting in both therapeutic resistance and cancer relapse. It is essential that we gain a fuller understanding of the complex networks involved in MPN cell biology and the role JAK2 plays in MPN pathogenesis. The purpose of this work is to use advanced mass spectrometry to further our understanding of the regulation of MPN cell biology, which will improve our ability to design better clinical therapies to treat these diseases.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
14/NW/1444
Date of REC Opinion
21 Nov 2014
REC opinion
Favourable Opinion