Re-evaluating the role of BCR/ABL in chronic myelogenous leukemia

Theodora S. Ross, Victoria E. Mgbemena

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Chronic myelogenous leukemia (CML) requires the BCR/ABL tyrosine kinase for disease onset and maintenance. As a result, CML can be successfully treated with tyrosine kinase inhibitors (TKIs) such as imatinib. Most patients are maintained in a disease-suppressed state on daily TKI therapy for several years and in many cases this treatment prevents progression to the blast phase. If the TKI is discontinued, CML redevelops in 95% of patients as a result of persisting leukemia initiating cells (LICs). There are several hypotheses that describe the potential mechanism(s) responsible for LIC persistence in CML, but supporting evidence is limited. Furthermore, of the few patients who discontinue TKI therapy and are “cured” (i.e., in treatment-free remission), most have residual BCR/ABL-expressing cells in their hematopoietic tissues. There are also healthy individuals without a CML diagnosis who express the BCR/ABL mutation in a fraction of their hematopoietic cells. Finally, mice that express BCR/ABL from the Bcr locus as a knockin mutation do not develop CML. These mice have lower BCR/ABL levels than retroviral or transgenic models of BCR/ABL that do develop CML. Understanding why mice with BCR/ABL expressed from the Bcr locus and some people that express BCR/ABL are not afflicted with CML will provide insights into therapies to prevent or cure this disease.

Original languageEnglish (US)
Article numbere963450
JournalMolecular and Cellular Oncology
Volume1
Issue number3
DOIs
StatePublished - Sep 15 2014

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Leukemia
Blast Crisis
Therapeutics
Mutation
Maintenance

Keywords

  • BCR/ABL
  • CML
  • hematopoiesis
  • imatinib
  • LIC

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine

Cite this

Re-evaluating the role of BCR/ABL in chronic myelogenous leukemia. / Ross, Theodora S.; Mgbemena, Victoria E.

In: Molecular and Cellular Oncology, Vol. 1, No. 3, e963450, 15.09.2014.

Research output: Contribution to journalArticle

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