The yin and yang-like clinical implications of the cdkn2a/arf/cdkn2b gene cluster in acute lymphoblastic leukemia
| Autor: | González Gil, Celia, Ribera Salas, Jordi, Ribera, Jose-Maria, Genescà, Eulàlia, Universitat Autònoma de Barcelona |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
lcsh:QH426-470 acute lymphoblastic leukemia Biology leukemogenesis Metastasis 03 medical and health sciences 0302 clinical medicine CDKN2A CDKN2B Gene cluster Genetics medicine Gene Genetics (clinical) Leukemogenesis treatment del(9p21.3) Cute lymphoblastic leukemia Cancer medicine.disease Prognosis Treatment Haematopoiesis lcsh:Genetics 030104 developmental biology 030220 oncology & carcinogenesis Cancer research prognosis Function (biology) Del(9p21.3) |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Genes, Vol 12, Iss 79, p 79 (2021) |
| Popis: | Altres ajuts: This project was supported by the Asociación Española Contra el Cáncer (AECC) (Project reference: GC16173697BIGA), Instituto de Salud Carlos III, CERCA Program/Generalitat de Catalunya. Acute lymphoblastic leukemia (ALL) is a malignant clonal expansion of lymphoid hematopoietic precursors that exhibit developmental arrest at varying stages of differentiation. Similar to what occurs in solid cancers, transformation of normal hematopoietic precursors is governed by a multistep oncogenic process that drives initiation, clonal expansion and metastasis. In this process, alterations in genes encoding proteins that govern processes such as cell proliferation, differentiation, and growth provide us with some of the clearest mechanistic insights into how and why cancer arises. In such a scenario, deletions in the 9p21.3 cluster involving CDKN2A/ARF/CDKN2B genes arise as one of the oncogenic hallmarks of ALL. Deletions in this region are the most frequent structural alteration in T-cell acute lymphoblastic leukemia (T-ALL) and account for roughly 30% of copy number alterations found in B-cell-precursor acute lymphoblastic leukemia (BCP-ALL). Here, we review the literature concerning the involvement of the CDKN2A/B genes as a prognosis marker of good or bad response in the two ALL subtypes (BCP-ALL and T-ALL). We compare frequencies observed in studies performed on several ALL cohorts (adult and child), which mainly consider genetic data produced by genomic techniques. We also summarize what we have learned from mouse models designed to evaluate the functional involvement of the gene cluster in ALL development and in relapse/resistance to treatment. Finally, we examine the range of possibilities for targeting the abnormal function of the protein-coding genes of this cluster and their potential to act as anti-leukemic agents in patients. |
| Databáze: | OpenAIRE |
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