ArticleHaematologica2023
Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials.
Article in Haematologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 10 citations in OpenAlex.
- A prognostic score system in adult T-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation.Bone marrow transplantation · 2024Trial
- Exploring coding and signal joints of novel TCR beta D-D rearrangements for tracking T-cell leukemia clonality.Experimental hematology & oncology · 2025Article
- Genetic evolution and relapse-associated mutations in adult T-cell acute lymphoblastic leukemia patients treated in PETHEMA trials.HemaSphere · 2025Article
- Diagnostic genomic analysis is prognostic in AYA patients with ALL treated on an MRD-stratified pediatric protocol.Blood neoplasia · 2025Article
- Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials.Haematologica · 2025Article
- Genetic hallmarks and clinical implications of chromothripsis in childhood T-cell acute lymphoblastic leukemia.Leukemia · 2024Article
- Article
- Should we perform baseline NGS testing in precursor T lymphoblastic leukaemias: a single centre experience from Eastern India.Ecancermedicalscience · 2024Article
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39 authors at 20 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
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 clinicalbiological 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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