[History of chronic myeloid leukemia: a paradigm in the treatment of cancer].
During two centuries, advances in medicine and medical research have helped to understand the pathophysiology of chronic myelogenous leukemia (CML). This hematologic malignancy is a unique model of oncogenesis where a single molecular hit, causing cell proliferation and survival, was identified. The chromosomal abnormality first highlighted by P. Nowell and D. Hungerford in 1960, and characterized as the reciprocal translocation t(9;22)(q34;q11), the Philadelphia chromosome, discovered in leukemic cells, by J. Rowley in 1973. At the end of the 20th century, the contribution of molecular biology techniques was crucial by the discovery of the BCR-ABL1 hybrid oncogene derived from the t(9;22), responsible for the translation of an aberrant protein tyrosine kinase. This BCR-ABL1 kinase deregulates signaling pathways that control normal cell cycle and survival in primitive hematopoietic cells and is thus responsible for malignant cell accumulation observed in CML. It was then only necessary to develop a targeted treatment adapted to this molecular hit. Recently, tyrosine kinase inhibitors, by their specific inhibitory activity of BCR-ABL, have revolutionized the treatment of CML, allowing rates of haematological, cytogenetic and molecular responses never seen to date, and has significantly improved the overall survival and the quality of life of patients.
Faculté de médecine Lyon-Est, Université Claude-Bernard Lyon 1, 8, Avenue Rockfeller 69373 Lyon cedex 08, France.
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Gonon-Demoulian
Department of Haematology, Imperial College at Hammersmith Hospital, Du Cane road, London, W12 0NN, United Kingdom, European Leukemia Net (ELN), III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim, der Ruprecht-Karls-Universität, Heidelberg, Pettenkoferstr. 22, D-68169 Mannheim, Allemagne.
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Goldman
Hématologie clinique 1G, Centre hospitalier Lyon-Sud, 165, chemin du Grand-Revoyet, 69495 Pierre Bénite cedex, France, France Intergroupe de la LMC (Fi-LMC), Université Victor, Segalen Bordeaux 2, 146 rue Leo Saignat, INSERM E217, 33076 Bordeaux cedex, France, European Leukemia Net (ELN), III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim, der Ruprecht-Karls-Universität, Heidelberg, Pettenkoferstr. 22, D-68169 Mannheim, Allemagne.
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Nicolini
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001151:Arsenic / Q000266:history / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000266:history; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000266:history / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000266:history / Q000379:methods; D010677:Philadelphia Chromosome; D011878:Radiotherapy; D014178:Translocation, Genetic
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl; D001151:Arsenic
CML; JH Bennett; R Virchow; allogeneic stem cell transplantation; interferon; tyrosine kinase inhibitors