Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells

Eliza Vakana, Ahmet Dirim Arslan, Amy Szilard, Jessica K. Altman, Leonidas C. Platanias

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are characterized by the presence of the BCR-ABL oncoprotein, which leads to activation of a plethora of pro-mitogenic and pro-survival pathways, including the mTOR signaling cascade. We provide evidence that in BCR-ABL expressing cells, treatment with tyrosine kinase inhibitors (TKIs) results in upregulation of mRNA levels and protein expression of sestrin3 (SESN3), a unique cellular inhibitor of mTOR complex 1 (mTORC1). Such upregulation appears to be mediated by regulatory effects on mTOR, as catalytic inhibition of the mTOR kinase also induces SESN3. Catalytic mTOR inhibition also results in upregulation of SESN3 expression in cells harboring the TKI-insensitive T315I-BCR-ABL mutant, which is resistant to imatinib mesylate. Overexpression of SESN3 results in inhibitory effects on different Ph+ leukemic cell lines including KT-1-derived leukemic precursors, indicating that SESN3 mediates anti-leukemic responses in Ph+ cells. Altogether, our findings suggest the existence of a novel mechanism for the generation of antileukemic responses in CML cells, involving upregulation of SESN3 expression.

Original languageEnglish (US)
Article numbere78780
JournalPloS one
Issue number11
StatePublished - Nov 18 2013

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General
  • General Biochemistry, Genetics and Molecular Biology


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