Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/124101
Title: Presence of Myeloid Mutations in Patients with Chronic Myeloid Leukemia Increases Risk of Cardiovascular Event on Tyrosine Kinase Inhibitor Treatment
Authors: Stuckey, Ruth
Segura Díaz, Adrian 
Sáez Perdomo, María Nieves
Pérez Encinas, Manuel Mateo
González San Miguel, Jóse David
Florido, Yanira
Sánchez Sosa, José Santiago 
López Rodríguez, Juan Francisco 
Bilbao Sieyro, Cristina 
Gómez Casares, María Teresa 
UNESCO Clasification: 320101 Oncología
Keywords: Cardiovascular Event
Chronic Myeloid Leukemia (Cml)
Clonal Hematopoiesis Of Indeterminate Potential (Chip)
Next-Generation Sequencing (Ngs)
Prognosis, et al
Issue Date: 2023
Journal: Cancers (Basel) 
Abstract: For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or dasatinib. To date, very few studies have evaluated the genetic predisposition associated with CVE development on TKI treatment. In this retrospective study of 102 CML patients, 26 CVEs were reported during an average follow-up of over 10 years. Next-generation sequencing identified pathogenic/likely pathogenic mutations in genes associated with myeloid malignancies in 24.5% of the diagnostic samples analyzed. Patients with a recorded CVE had more myeloid mutations (0.48 vs. 0.14, p = 0.019) and were older (65.1 vs. 55.7 years, p = 0.016). Age ≥ 60 years and receiving a 2G-TKI in first-line were CVE risk factors. The presence of a pathogenic somatic myeloid mutation was an independent risk factor for CVE on any TKI (HR 2.79, p = 0.01), and significantly shortened the CV event-free survival of patients who received first-line imatinib (by 70 months, p = 0.011). Indeed, 62% of patients on imatinib with mutations had a CVE vs. the 19% on imatinib with a mutation and no CVE. In conclusion, myeloid mutations detectable at diagnosis increase CVE risk, particularly for patients on imatinib, and might be considered for first-line TKI choice.
URI: http://hdl.handle.net/10553/124101
DOI: 10.3390/cancers15133384
Source: Cancers [EISSN 2072-6694], v. 15 (13), (Julio 2023)
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