1. Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey.
- Author
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Hofer KD, Bühler MM, Roncador M, Rechsteiner M, Maggio EM, Tchinda J, Schanz U, Haralambieva E, and Widmer CC
- Subjects
- Humans, Male, Adult, Female, Middle Aged, Young Adult, Aged, Neoplasms, Second Primary genetics, Neoplasms, Second Primary etiology, Neoplasms, Second Primary therapy, Adolescent, Prognosis, Gene Rearrangement, Myeloid-Lymphoid Leukemia Protein genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Mutation
- Abstract
There is increasing evidence that therapy-related acute lymphoblastic leukemia (trALL) resulting from chemo- and/or radiotherapy represents a distinct entity. However, apart from KMT2A rearrangements, which have been repeatedly reported in this subgroup, the relevance of other aberrations remains controversial due to divergent study results and sparse molecular analyses. Within our ALL patient cohort, 15% ( n = 19/131) met the criteria for trALL with a high proportion of Ph + and KMT2A rearrangements. On the molecular level, the most frequently observed mutation was KMT2D , followed by CDKN2A , KRAS and DNMT3A . No TP53 mutation was detected. Outcome was particularly poor in Ph + trALL compared to Ph+ de novo ALL, which seemed to be mitigated by allogeneic stem cell transplantation. Our findings further define trALL as a distinct entity but highlight the need for further molecular genome sequencing of somatic and germline variants to advance our understanding of trALL.
- Published
- 2024
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