Targeting Plek2 as a Novel Approach for the Treatment of Myeloproliferative Neoplasms

Project: Research project

Project Details

Description

Myeloproliferative neoplasms (MPNs) are a group of bone marrow diseases with
excessive myeloid cell production and increased risk of evolving to acute myeloid
leukemia. V617F driver mutation of JAK2 is one of the leading causes of MPNs. The
discovery of this mutation led to the development of JAK inhibitors for the treatment of
MPNs. However, JAK2 inhibitors are not curative. In addition, MPN patients treated with
JAK2 inhibitor often develop drug resistance and severe side effects due to the
indispensable roles of JAK2 in normal blood cell development. We have been studying
new approaches to treating MPNs, especially focusing on the downstream effectors of
the JAK2 pathway. Our preliminary studies revealed that loss of Plek2, which is a novel
downstream target of the JAK2 pathway, ameliorated JAK2V617F-induced
myeloproliferative phenotypes, and more significantly reverted the widespread vascular
occlusions and lethality of JAK2V617F MPN mouse model. In this proposal, we will use our
newly designed small molecular Plek2 inhibitors to treat MPN mouse model and bone
marrow progenitor cells from MPN patients. Successful completion of this project will lay
the foundation for clinical trials of using Plek2 inhibitors as single agents or in
combination with other compounds to treat MPNs.
StatusFinished
Effective start/end date1/1/1712/31/17

Funding

  • Northwestern Memorial Hospital (NMH 04/03/2017)

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