Chronic myeloid leukemia (CML) was transformed from a fatal disease to a chronic condition by the development of a drug known as imatinib, which targets the protein that drives this disease (BCR-ABL). However, imatinib does not cure patients, they must take the drug lifelong, as disease recurs if they stop taking it. This is because imatinib does not kill all the CML cells; some, which are known as CML stem cells, persist. A key to therapeutically targeting CML stem cells is knowing whether they rely on BCR-ABL to persist. Answers to this will determine whether more effective BCR-ABL inhibitors are likely to be effective treatments or whether new approaches to targeting these cells need to be developed.
A team of researchers, led by Brian Drucker and Michael Deininger, at Oregon Health and Science University, Portland, has now shown clearly that human CML stem cells do not depend on BCR-ABL activity for survival and are thus not eliminated by imatinib therapy. As noted by the authors and, in an accompany commentary, Alexander Perl and Martin Carroll, at the University of Pennsylvania, Philadelphia, the data indicate that therapeutics targeting BCR-ABL will not improve CML treatment and that new approaches are needed if further advances in patient care are to be made.
TITLE: Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity
AUTHOR CONTACT:
Michael W. Deininger
Oregon Health and Science University, Portland, Oregon, USA.
Phone: 503.494.1091; Fax: 503.494.3688; E-mail: deinginge@ohsu.edu .
Brian J. Druker,
Oregon Health and Science University, Portland, Oregon, USA.
Phone: 503.494.1288; Fax: 503.494.3688; E-mail: drukerb@ohsu.edu .
View this article at: http://www.jci.org/articles/view/35721?key=1602b640084adb5cfcdc
ACCOMPANYING COMMENTARY
TITLE: BCR-ABL kinase is dead; long live the CML stem cell
AUTHOR CONTACT:
Martin Carroll
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215.573.5217; Fax: 215.573.7049; E-mail: carroll2@mail.med.upenn.edu .
View this article at: http://www.jci.org/articles/view/43605?key=1da0d8726712d0c91c88
Journal of Clinical Investigation