The yin and yang-like clinical implications of the cdkn2a/arf/cdkn2b gene cluster in acute lymphoblastic leukemia
González Gil, Celia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribera Salas, Jordi (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Genescà, Eulàlia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-288 Instituto de Salud Carlos III PI14-01971
Note:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article de revisió ; Article ; Versió publicada
Subject:	Cute lymphoblastic leukemia ; Del(9p21.3) ; Leukemogenesis ; Prognosis ; Treatment
Published in:	Genes, Vol. 12 Núm. 1 (january 2021) , p. 1-27, ISSN 2073-4425

DOI: 10.3390/genes12010079
PMID: 33435487

27 p, 659.3 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Published articles