Influence of Telomere Length on the Achievement of Deep Molecular Response With Imatinib in Chronic Myeloid Leukemia Patients

Abstract

Leucèmia mieloide crònica; Resposta a imatinib; Telòmer

Leucemia mieloide crónica; Respuesta a imatinib; Telómero

Chronic myelogenous leukemia; Imatinib; Telomere

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 (P = 0.035 when delta-TL was studied as a continuous variable and P = 0.047 when categorized by the median). Moreover, patients carrying long telomeres also achieved major molecular response significantly earlier (P = 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.

This work was in part supported by a grant from Instituto de Salud Carlos III through the project “PI16/01200” (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/”Investing in your future”) as well as by the grant “Bolsa de ayuda económica para la innovación científica” and the grant “Becas de Investigación” both from Fundación Española de Hematología y Hemoterapia (FEHH). Figure 3. Cumulative incidence (95% CI) of MMR at 24 months from imatinib start. CI = confidence interval Downloaded from http://journals.lww.com/hemasphere by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/