Estrada Natalia, Xicoy Blanca, Beier Fabian, Garcia Olga, Morales Cristian, Boqué Concepción, Sagüés Miguel, Ventura Ferreira Mónica S, Vallansot Rolando, Marcé Sílvia, Cabezón Marta, Brümmendorf Tim H, Zamora Lurdes
Myeloid Neoplasms Research Group, Josep Carreras Leukemia Research Institute, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Spain.
Hematology Department, Institut Català d'Oncologia (ICO)-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, Spain.
Hemasphere. 2021 Nov 30;5(12):e657. doi: 10.1097/HS9.0000000000000657. eCollection 2021 Dec.
Tyrosine kinase inhibitors have dramatically changed the outcome of chronic myeloid leukemia (CML), and nowadays, one of the main treatment goals is the achievement of deep molecular responses (DMRs), which can eventually lead to therapy discontinuation approaches. Few biological factors at diagnosis have been associated with this level of response. Telomere length (TL) in peripheral blood cells of patients with CML has been related to disease stage, response to therapy and disease progression, but little is known about its role on DMR. In this study, we analyzed if age-adjusted TL (referred as "delta-TL") at diagnosis of chronic phase (CP)-CML might correlate with the achievement of DMR under first-line imatinib treatment. TL from 96 CP-CML patients had been retrospectively analyzed at diagnosis by monochrome multiplex quantitative PCR. We observed that patients with longer age-adjusted telomeres at diagnosis had higher probabilities to achieve DMR with imatinib than those with shortened telomeres ( = 0.035 when delta-TL was studied as a continuous variable and = 0.047 when categorized by the median). Moreover, patients carrying long telomeres also achieved major molecular response significantly earlier ( = 0.012). This study provides proof of concept that TL has a role in CML biology and when measured at diagnosis of CP-CML could help to identify patients likely to achieve DMR to first-line imatinib treatment.
酪氨酸激酶抑制剂极大地改变了慢性髓性白血病(CML)的治疗结果,如今,主要治疗目标之一是实现深度分子反应(DMRs),这最终可能会带来治疗中断方案。诊断时很少有生物学因素与这种反应水平相关。CML患者外周血细胞中的端粒长度(TL)与疾病阶段、对治疗的反应及疾病进展有关,但关于其在DMR中的作用知之甚少。在本研究中,我们分析了慢性期(CP)-CML诊断时的年龄校正端粒长度(称为“delta-TL”)是否与一线伊马替尼治疗下DMR的实现相关。通过单色多重定量PCR对96例CP-CML患者诊断时的TL进行了回顾性分析。我们观察到,诊断时年龄校正端粒较长的患者使用伊马替尼实现DMR的概率高于端粒缩短的患者(将delta-TL作为连续变量研究时P = 0.035,按中位数分类时P = 0.047)。此外,携带长端粒的患者也显著更早地实现了主要分子反应(P = 0.012)。本研究提供了概念验证,即TL在CML生物学中起作用,在CP-CML诊断时进行测量有助于识别可能对一线伊马替尼治疗实现DMR的患者。