Sorel Nathalie, Cayssials Émilie, Brizard Françoise, Chomel Jean-Claude
Service de cancérologie biologique, CHU de Poitiers, Poitiers, France.
Service d'oncologie hématologique et thérapie cellulaire, CHU de Poitiers, Poitiers, France.
Ann Biol Clin (Paris). 2017 Apr 1;75(2):129-145. doi: 10.1684/abc.2017.1233.
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.
慢性髓系白血病（CML）是一种由t(9;22)(q34;q11)易位导致的骨髓增殖性肿瘤。其特征是存在编码BCR-ABL癌蛋白的BCR-ABL1融合基因，该蛋白具有失调的酪氨酸激酶活性。使用酪氨酸激酶抑制剂（TKI）如伊马替尼、达沙替尼、尼洛替尼、博舒替尼或普纳替尼进行的靶向治疗已深刻改变了该疾病的自然病程，对生存率产生了重大影响。事实上，如今大多数被诊断出的患者能够享有接近正常的预期寿命。TKI治疗的疗效可通过基于BCR-ABL1 mRNA转录本定量和检测BCR-ABL激酶结构域耐药突变的分子监测来准确评估。关于使用生物学参数对CML进行优化管理的国际建议定期发布。这些建议旨在评估治疗反应，并在必要时考虑换用另一种TKI。相当比例的患者获得了持续且深度的分子反应。在这类人群中进行了TKI停药的临床试验，一半的患者未复发。在其余患者中，观察到恶性克隆迅速出现，这无疑是残留白血病干细胞（LSC）持续存在的结果。如何鉴别哪些患者可以安全停用TKI？如何靶向残留的LSC，以及我们是否必须根除所有这些细胞？为了考虑CML的潜在治愈，需要进行更多的研究调查和临床试验来回答这些问题。
