TitleExovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes.
Publication TypeJournal Article
Year of Publication2021
AuthorsDalal H, Subramanian S, P SV, Gowda DA, H K, Damodar S, Vyas N
JournalCell Death Dis
Volume12
Issue3
Pagination259
Date Published2021 Mar 11
ISSN2041-4889
Abstract

Chronic myeloid leukemia (CML) patients with complex chromosomal translocations as well as non-compliant CML patients often demonstrate short-lived responses and poor outcomes on the current therapeutic regimes using Imatinib and its variants. It has been derived so far that leukemic stem cells (LSCs) are responsible for Imatinib resistance and CML progression. Sonic hedgehog (Shh) signaling has been implicated in proliferation of this Imatinib-resistant CD34(+) LSCs. Our work here identifies the molecular mechanism of Shh-mediated mutation-independent Imatinib resistance that is most relevant for treating CML-variants and non-compliant patients. Our results elucidate that while Shh can impart stemness, it also upregulates expression of anti-apoptotic protein-Bcl2. It is the upregulation of Bcl2 that is involved in conferring Imatinib resistance to the CD34(+) LSCs. Sub-toxic doses of Bcl2 inhibitor or Shh inhibitor (

DOI10.1038/s41419-021-03542-w
Alternate JournalCell Death Dis
PubMed ID33707419
Grant ListBT/PR26240/BRB/10/1626/2017 / / Department of Biotechnology, Ministry of Science and Technology (DBT) /
CRG/2019/005347 / / DST | Science and Engineering Research Board (SERB) /
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