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- Title
Comprehensive characterization of a novel, oncogenic and targetable SEPTIN6::ABL2 fusion in T‐ALL.
- Authors
Lahera, Antonio; Vela‐Martín, Laura; López‐Nieva, Pilar; Salgado, Rocío N.; Rodríguez‐Perales, Sandra; Torres‐Ruiz, Raúl; López‐Lorenzo, José L.; Cornago, Javier; Llamas, Pilar; Fernández‐Navarro, Pablo; Sánchez‐Domínguez, Rebeca; Segovia, José C.; Sastre, Isabel; Cobos‐Fernández, María Á.; Menéndez, Pablo; Santos, Javier; Fernández‐Piqueras, José; Villa‐Morales, María
- Abstract
(E) Cell growth analysis of Jurkat, K562 and Ba/F3 cells transduced with SEPTIN6:ABL2 (Ba/F3-SA) treated with Imatinib (0.1, 0.5 or 1 M; left), Nilotinib (10, 50, 100 nM; middle) and Dasatinib (1, 5, 10 nM; right) and referred to DMSO-treated cells. T-cell acute lymphoblastic leukaemia (T-ALL) arises from the malignant transformation of T-cell progenitors.[[1]] Current standard-of-care treatment for T-ALL consists of high-dose multi-agent chemotherapy followed by haematopoietic stem cell transplantation (HSCT) in standard-high risk patients.[3] Despite reasonable rates of initial complete responses (CR), patients who relapse or do not respond to first-line treatments show a dismal outcome with cure rates below 10% and limited therapeutic options.[2] Actually, since the approval of nelarabine in 2005 no pharmacological inhibitors have been approved for relapsed/refractory T-ALL patients.[4] Therefore, there is an urgent need to identify the molecular alterations that are present in such patients and that promote leukemogenesis in order to implement personalized-therapies with higher efficacy and fewer adverse effects.[5] Here, we identify and comprehensively characterize a novel, oncogenic and targetable I SEPTIN6 i : I ABL2 i fusion in a 16-year-old boy with T-ALL (Figure 1A). M07e cells transduced with I SEPTIN6 i : I ABL2 i showed significantly higher levels of cell growth and viability compared to cells transduced with the empty-vector or with I ABL2 i SP WT sp in the absence of cytokines (Figure 2A). We evaluated the mutational profile of the patient in matched tumour samples at diagnosis (Patient Dx) and relapse (Patient Rx) by paired-end 2 × 150 bp exome sequencing analysis.
- Subjects
HEMATOPOIETIC stem cell transplantation; TUMOR suppressor genes
- Publication
British Journal of Haematology, 2023, Vol 202, Issue 3, p693
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.18901