TY - JOUR
T1 - Eradication of leukemia stem cells as a new goal of therapy in leukemia
AU - Ravandi, Farhad
AU - Estrov, Zeev
PY - 2006/1/15
Y1 - 2006/1/15
N2 - Leukemias have traditionally been classified and treated on the basis of phenotypic characteristics, such as morphology and cell-surface markers, and, more recently, cytogenetic aberrations. These classification systems are flawed because they do not take into account cellular function. The leukemia cell population is functionally heterogeneous: it consists of leukemia stem cells (LSC) and mature leukemia cells that differentiate abnormally to varying extents. Like normal hematopoietic stem cells, LSCs are quiescent and have self-renewal and clonogenic capacity. Because they are quiescent, LSCs do not respond to cell cycle-specific cytotoxic agents used to treat leukemia and so contribute to treatment failure. These cells may undergo mutations and epigenetic changes, further leading to drug resistance and relapse. Recent data suggest that mature leukemia cells may acquire LSC characteristics, thereby evading chemotherapeutic treatment and sustaining the disease. Ongoing research is likely to reveal the molecular mechanisms responsible for LSC characteristics and lead to novel strategies for eradicating leukemia.
AB - Leukemias have traditionally been classified and treated on the basis of phenotypic characteristics, such as morphology and cell-surface markers, and, more recently, cytogenetic aberrations. These classification systems are flawed because they do not take into account cellular function. The leukemia cell population is functionally heterogeneous: it consists of leukemia stem cells (LSC) and mature leukemia cells that differentiate abnormally to varying extents. Like normal hematopoietic stem cells, LSCs are quiescent and have self-renewal and clonogenic capacity. Because they are quiescent, LSCs do not respond to cell cycle-specific cytotoxic agents used to treat leukemia and so contribute to treatment failure. These cells may undergo mutations and epigenetic changes, further leading to drug resistance and relapse. Recent data suggest that mature leukemia cells may acquire LSC characteristics, thereby evading chemotherapeutic treatment and sustaining the disease. Ongoing research is likely to reveal the molecular mechanisms responsible for LSC characteristics and lead to novel strategies for eradicating leukemia.
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U2 - 10.1158/1078-0432.CCR-05-1879
DO - 10.1158/1078-0432.CCR-05-1879
M3 - Review article
C2 - 16428470
AN - SCOPUS:31544456409
SN - 1078-0432
VL - 12
SP - 340
EP - 344
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -