John Libbey Eurotext

Annales de Biologie Clinique


Treatment and molecular monitoring update in chronic myeloid leukemia management Volume 75, issue 2, Mars-Avril 2017


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1 Service de cancérologie biologique, CHU de Poitiers, Poitiers, France
2 Service d’oncologie hématologique et thérapie cellulaire, CHU de Poitiers, Poitiers, France
3 Service d’hématologie biologique, CHU de Poitiers, Poitiers, France
* Tirés à part

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the t(9;22)(q34;q11) translocation. It is characterized by the presence of the BCR-ABL1 fusion gene encoding the BCR-ABL oncoprotein characterized by a deregulated tyrosine kinase activity. Targeted therapies using tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib, bosutinib, or ponatinib have profoundly changed the natural history of the disease with a major impact on survival. Indeed, most patients diagnosed today can enjoy a near normal life expectancy. The efficacy of TKI treatment can be accurately evaluated by a molecular monitoring based on the quantification of BCR-ABL1 mRNA transcripts and the detection of resistance mutations in the BCR–ABL kinase domain. International recommendations for an optimal management of CML using biological parameters are regularly published. They were designed to evaluate the response to the treatment and to consider, if necessary, a switch to another TKI. A sustained and deep molecular response is obtained in a significant percentage of patients. Clinical trials of TKI discontinuation were performed in such a population, and half of patients do not relapse. In the remaining patients, a rapid appearance of the malignant clone was observed, undoubtedly the consequence of the persistence of residual leukemic stem cells (LSCs). How to discriminate patients who may safely stop TKI? How to target residual LSCs, and do we have to eradicate all these cells? Additional research investigation and clinical trials are needed to answer these questions in order to consider a potential cure of CML.