Getting to the stem of chronic myeloid leukaemia.
Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia (CML) is the consummate success story for targeted therapy, yet relapse is a nearly inevitable consequence of cessation or interruption of therapy. Primitive TKI-refractory CML stem cells are the likely source of these relapses, as they provide sanctuary for the Philadelphia chromosome. In advanced disease, their progressively anaplastic progeny ultimately maintain CML independently of the CML haematopoietic stem cell (HSC). Interestingly, there are at least two distinct cell types capable of self-renewal in different phases of CML: first, a primitive HSC with BCR-ABL mutation, which maintains the more indolent chronic-phase disease and, second, a coexisting mutated progenitor cell which acquires stem cell characteristics responsible for rapid cell expansion in advanced disease.
Savona
Michael
M
University of Michigan, Internal Medicine-Hematology Oncology, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-45936, USA. msavona@med.umich.edu
Talpaz
Moshe
M
D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use; D025521:Tumor Suppressor Proteins / Q000235:genetics
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D025521:Tumor Suppressor Proteins; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl