Novel combination treatments targeting chronic myeloid leukemia stem cells

Tareq Al Baghdadi, Rafat Abonour, H. Boswell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Chronic myeloid leukemia (CML) is currently considered incurable in most patients. Stem cell transplantation, an accepted curative option for which extensive experience has been gained, is limited by high morbidity and mortality rates, particularly in older patients. Tyrosine kinase inhibitors targeting BCR-ABL are widely used and induce remission in a high proportion of patients, but resistance and incomplete response to these agents portends eventual relapse and disease progression. Although BCR-ABL inhibitors eradicate most CML cells, they are largely ineffective against the reservoir of quiescent leukemic stem cells (LSCs). Thus a strong medical need exists for therapies that effectively eradicate LSCs and is currently a focus of extensive research. To date, evidence obtained from in vitro studies, animal models, and clinical CML specimens suggests that an effective approach may be to partner existing BCR-ABL inhibitors with compounds targeting key stem cell molecular effectors, including Wnt/β-catenin, hedgehog pathway components, histone deacetylase (HDAC), transforming growth factor-β (TGF-β), Janus kinase 2, promyelocytic leukemia protein, and arachidonate 5-lipoxygenase (ALOX5). Novel combinations may sensitize LSCs to BCR-ABL inhibitors, thereby overcoming resistance and creating the possibility of improving disease outcome beyond the current standard of care.

Original languageEnglish
Pages (from-to)94-105
Number of pages12
JournalClinical Lymphoma, Myeloma and Leukemia
Volume12
Issue number2
DOIs
StatePublished - Apr 2012

Fingerprint

Myeloid Progenitor Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Stem Cells
Janus Kinase 2
Arachidonate 5-Lipoxygenase
Catenins
Histone Deacetylases
Transforming Growth Factors
Stem Cell Transplantation
Myeloid Cells
Therapeutics
Standard of Care
Protein-Tyrosine Kinases
Disease Progression
Animal Models
Morbidity
Recurrence
Mortality
Research

Keywords

  • BCR-ABL inhibitors
  • Chronic myeloid leukemia
  • Dasatinib
  • Imatinib
  • Nilotinib
  • Progenitor cells
  • Stem cells
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Novel combination treatments targeting chronic myeloid leukemia stem cells. / Al Baghdadi, Tareq; Abonour, Rafat; Boswell, H.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 12, No. 2, 04.2012, p. 94-105.

Research output: Contribution to journalArticle

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