Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia.
Standard allogeneic stem cell transplantation (alloSCT) has provided a cure for chronic myeloid leukaemia (CML) over the last 25 years, but is only an option for a minority of patients. It was hoped that the introduction of imatinib mesylate (IM), a specific tyrosine kinase inhibitor that targets the Bcr-Abl oncogene product, would provide long-term remission or even cure for those patients without a donor, but studies have shown that IM does not eliminate leukaemic stem cells in CML patients. To overcome this problem of molecular persistence, research is underway to combine reduced intensity stem cell transplant or non-donor-dependent immunotherapies with IM with the aim of increasing cure rate, reducing toxicity and improving quality of life. The alternative approach is to combine IM or second-generation agents with other novel drugs that interrupt key signalling pathways activated by Bcr-Abl. This article will focus on the latest immunotherapy and molecularly targeted therapeutic options in CML and how they may be combined to improve the outcome for CML patients in the future.
Copland
M
M
ATMU, Section of Experimental Haematology, University Faculty of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, UK.
Fraser
A R
AR
Harrison
S J
SJ
Holyoake
T L
TL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D003713:Dendritic Cells / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D007167:Immunotherapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl