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Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins

T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia an...

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Detalles Bibliográficos
Autores principales: Steimlé, Thomas, Dourthe, Marie-Emilie, Alcantara, Marion, Touzart, Aurore, Simonin, Mathieu, Mondesir, Johanna, Lhermitte, Ludovic, Bond, Jonathan, Graux, Carlos, Grardel, Nathalie, Cayuela, Jean-Michel, Arnoux, Isabelle, Gandemer, Virginie, Balsat, Marie, Vey, Norbert, Macintyre, Elizabeth, Ifrah, Norbert, Dombret, Hervé, Petit, Arnaud, Baruchel, André, Ruminy, Philippe, Boissel, Nicolas, Asnafi, Vahid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791998/
https://www.ncbi.nlm.nih.gov/pubmed/35082269
http://dx.doi.org/10.1038/s41408-022-00613-9
Descripción
Sumario:T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases. PICALM-MLLT10 (4%, n = 23), NUP214-ABL1 (3%, n = 19) and SET-NUP214 (3%, n = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63; p = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6; p = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.