Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence

Shoichiro Takeishi, Akinobu Matsumoto, Ichiro Onoyama, Kazuhito Naka, Atsushi Hirao, Keiichi Nakayama

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Imatinib eradicates dividing progenitor cells of chronic myeloid leukemia (CML) but does not effectively target nondividing leukemia-initiating cells (LICs); thus, the disease often relapse after its discontinuation. We now show that Fbxw7 plays a pivotal role in maintenance of quiescence in LICs of CML by reducing the level of c-Myc. Abrogation of quiescence in LICs by Fbxw7 ablation increased their sensitivity to imatinib, and the combination of Fbxw7 ablation with imatinib treatment resulted in a greater depletion of LICs than of normal hematopoietic stem cells in mice. Purging of LICs by targeting Fbxw7 to interrupt their quiescence and subsequent treatment with imatinib may thus provide the basis for a promising therapeutic approach to CML.

Original languageEnglish
Pages (from-to)347-361
Number of pages15
JournalCancer Cell
Volume23
Issue number3
DOIs
Publication statusPublished - Mar 18 2013

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Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematopoietic Stem Cells
Stem Cells
Maintenance
Recurrence
Imatinib Mesylate
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence. / Takeishi, Shoichiro; Matsumoto, Akinobu; Onoyama, Ichiro; Naka, Kazuhito; Hirao, Atsushi; Nakayama, Keiichi.

In: Cancer Cell, Vol. 23, No. 3, 18.03.2013, p. 347-361.

Research output: Contribution to journalArticle

Takeishi, Shoichiro ; Matsumoto, Akinobu ; Onoyama, Ichiro ; Naka, Kazuhito ; Hirao, Atsushi ; Nakayama, Keiichi. / Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence. In: Cancer Cell. 2013 ; Vol. 23, No. 3. pp. 347-361.
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