Genomics improves risk stratifi cation of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measur...

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Detalles Bibliográficos
Autores: González-Gil, C., Morgades, M., Lopes, T., Fuster-Tormo, F., García-Chica, J., Zhao, R., Montesinos, P., Torrent, A., Diaz-Beya, M., Coll, R., Hermosín, L., Mercadal, S., González-Campos, J., Zamora, L., Artola, T., Vall-Llovera, F., Tormo, M., Gil-Cortés, C., Barba, P., Novo Domínguez, Alejandro, Ribera, J., Bernal, T., de Ugarriza, P.L., Queipo, M.-P., Martínez-Sánchez, P., Giménez, A., González Martínez, María Teresa, Cladera, A., Cervera, J., Fernández-Martín, R., Ardaiz, M.Á., Vidal, M.J., Baena, Á., López-Bigas, N., Bigas, A., Maciejewski, J., Orfao, A., Ribera, J.M., Genescà, E.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21539
Acceso en línea:https://portalcientifico.sergas.gal//documentos/643af6e21656ab66db7e0f6f
http://hdl.handle.net/20.500.11940/21539
Access Level:acceso abierto
Palabra clave:Humans
Adult
Aged
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Prognosis
Neoplasm, Residual
Genomics
T-Lymphocytes
AS Santiago
CHUS
FPGMX
Descripción
Sumario:Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinical-biological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5-year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

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