Towards cure of CML: why we need to know more about CML stem cells?
The introduction of tyrosine kinase inhibitor treatment for CML marks one of the major success stories in the recent history of medicine. However, eradication of disease is almost never attained, because, unlike the vast majority of more differentiated cells, leukemic stem cells withstand TKI's, neccessitating life-long treatment. Besides, although a relatively infrequent event under treatment with TKI's, refractory leukemic stem cells may sometimes give rise to disease transformation. In this article, we will review the definitions of CML stem cells, explain how BCR-ABL induces perturbations of critical signal transduction pathways and summarize specific characteristics that cause refractoriness of CML stem cells against TKI's. Furthermore, events that are responsible or related to transformation of the disease into blast crisis will be discussed and new research directions that should lead to successful ways to attack leukemic stem cells are proposed.
Janssen
Jeroen J W M
JJ
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands. jjwm.janssen@vumc.nl
Schuurhuis
Gerrit J
GJ
Terwijn
Monique
M
Ossenkoppele
Gerrit J
GJ
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D053612:Janus Kinases / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000503:physiopathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D053612:Janus Kinases