BMB Reports Papers in Press available online.

Search Papers In Press
This galley proof is being listed electronically before publishing the final manuscript (It's not final version).

 
Hypoxia inducible factor 1メ inhibitor induces cell death via suppression of BCR-ABL1 and Met expression in BCR-ABL1 tyrosine kinase inhibitor sensitive and resistant chronic myeloid leukemia cells
Masanobu Tsubaki 1 (associate professor), Tomoya Takeda1 (assistant professor), Takuya Matsuda1 (Graduate student), Akihiro Kimura1 (Graduate student), Remi Tanaka1 (Graduate student), Sakiko Nagayoshi1 (College student), Tadafumi Hoshida1,2 (Graduate student), Kazufumi Tanabe2 (Research worker), Shozo Nishida 1,* (Professor)
1Division of Pharmacotherapy, Kindai University Faculty of Pharmacy,
2Department of Pharmacy, Japanese Red Cross Society Wakayama Medical Center
Abstract
Chronic myeloid leukemia (CML) has a markedly improved prognosis with the use of breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitors (BCR-ABL1 TKIs). However, approximately 40% of patients are resistant or intolerant to BCR-ABL1 TKIs. Hypoxia inducible factor 1メ (HIF-1メ) is a hypoxia response factor that has been reported to be highly expressed in CML patients, making it a candidate target molecule for the therapy of CML as well as BCR-ABL1 TKI-resistant CML. In this study, we examined whether HIF-1メ inhibitors induce cell death in CML cells and BCR-ABL1 TKI-resistant CML cells. We found that echinomycin and PX-478 induced cell death in BCR-ABL1 TKIs sensitive and resistant CML cells at similar concentrations while the cell sensitivity was not affected with imatinib or dasatinib in BCR-ABL1 TKIs resistant CML cells. In addition, echinomycin and PX-478 inhibited the c-Jun N-terminal kinase (JNK), Akt, and extracellular-regulated protein kinase 1/2 (ERK1/2) activation via suppression of BCR-ABL1 and Met expression in BCR-ABL1 sensitive and resistant CML cells. Moreover, treatment with HIF-1メ siRNA induced cell death by inhibiting BCR-ABL1 and Met expression and activation of JNK, Akt, and ERK1/2 in BCR-ABL1 TKIs sensitive and resistant CML cells. These results indicated that HIF-1メ regulates BCR-ABL and Met expression and is involved in cell survival in CML cells, suggesting that HIF-1メ inhibitors induce cell death in BCR-ABL1 TKIs sensitive and resistant CML cells. These findings suggest that HIF-1メ inhibitors may be beneficial as treatment for CML.
Abstract, Accepted Manuscript(in press) [Submitted on June 11, 2022, Accepted on September 16, 2022]
  Copyright © KSBMB. All rights reserved. / Powered by INFOrang Co., Ltd