Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 121, Issue 1, Pages 396-409Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI35721
Keywords
-
Categories
Funding
- Leukemia and Lymphoma Society [7393 06]
- Specialized Center of Research
- NHLBI [HL082978 01]
- Department of Defense [CM050037]
- T J Martell Foundation
- Lady Tata memorial trust
- Knight Cancer Center
- NATIONAL CANCER INSTITUTE [R37CA065823] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL082978] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Imatinib therapy, which targets the oncogene product BCR-ABL, has transformed chronic myeloid leukemia (CML) from a life-threatening disease into a chronic condition Most patients, however, harbor residual leukemia cells, and disease recurrence usually occurs when imatinib is discontinued Although various mechanisms to explain leukemia cell persistence have been proposed, the critical question from a therapeutic standpoint whether disease persistence is BCR-ABL dependent or independent has not been answered Here, we report that human CML stem cells do not depend on BCR-ABL activity for survival and are thus not eliminated by imatinib therapy Imatinib inhibited BCR-ABL activity to the same degree in all stem (CD34(+)CD38(-), CD133(+)) and progenitor (CD34(+)CD38(+)) cells and in quiescent and cycling progenitors from newly diagnosed CML patients Although short-term in vitro imatinib treatment reduced the expansion of CML stem/progenitors, cytokine support permitted growth and survival in the absence of BCR-ABL activity that was comparable to that of normal stem/progenitor counterparts Our findings suggest that primitive CML cells are not oncogene addicted and that therapies that biochemically target BCR-ABL will not eliminate CML stem cells
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available