Unknown

Dataset Information

0

HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis.


ABSTRACT: Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F model, in fibrosis. HSP27 regulates the proliferation of JAK2V617F-positive cells and interacts directly with JAK2/STAT5. We also show that its expression is increased in both CD34+ circulating progenitors and in the serum of patients with JAK2-dependent myeloproliferative neoplasms with fibrosis. Our data suggest that HSP27 plays a key role in the pathophysiology of myelofibrosis and represents a new potential therapeutic target for patients with myeloproliferative neoplasms.

SUBMITTER: Sevin M 

PROVIDER: S-EPMC5897330 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications


Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte  ...[more]

Similar Datasets

| S-EPMC5824979 | biostudies-other
| S-EPMC5615205 | biostudies-literature
| S-EPMC6445677 | biostudies-literature
| S-EPMC3618591 | biostudies-literature
| S-EPMC6739355 | biostudies-literature
| S-EPMC5840758 | biostudies-other
| S-EPMC8034969 | biostudies-literature
2022-08-11 | E-MTAB-11653 | biostudies-arrayexpress
| S-EPMC7244621 | biostudies-literature
| S-EPMC5778911 | biostudies-literature