Characterisation of cells markers associated with IKZF1 plus in BCP-ALL.

Autor:	Blunck CB; Genetics of Acute Leukaemia Laboratory-GenLAb, Research and Innovation Coordination, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37, 6th floor, Rio de Janeiro, RJ 20231-050, Brazil., Poubel CP; Genetics of Acute Leukaemia Laboratory-GenLAb, Research and Innovation Coordination, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37, 6th floor, Rio de Janeiro, RJ 20231-050, Brazil., Lopes BA; Genetics of Acute Leukaemia Laboratory-GenLAb, Research and Innovation Coordination, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37, 6th floor, Rio de Janeiro, RJ 20231-050, Brazil., Barbosa TC; Genetics of Acute Leukaemia Laboratory-GenLAb, Research and Innovation Coordination, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37, 6th floor, Rio de Janeiro, RJ 20231-050, Brazil., Maciel ALT; Genetics of Acute Leukaemia Laboratory-GenLAb, Research and Innovation Coordination, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37, 6th floor, Rio de Janeiro, RJ 20231-050, Brazil., da Costa ES; Department of Paediatrics, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Figueiredo ADR; Onco-Haematology Section, Prontobaby Hospital da Criança Ltda, Rio de Janeiro, RJ, Brazil., Land MGP; Department of Paediatrics, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology-INCT BioOncoPed, Porto Alegre 90035-003, Brazil., Schramm MT; Onco-Haematology Section, Prontobaby Hospital da Criança Ltda, Rio de Janeiro, RJ, Brazil; Haematology Unit, Hospital do Câncer I, Instituto Nacional de Câncer-INCA, Rio de Janeiro, RJ, Brazil., Ikoma-Coltutato MRV; Sabin Medicina Diagnóstica, Brasília, DF, Brazil., Gomes RG; Paediatric Oncology Unit, Instituto de Medicina Integral Prof Fernando Figueira, Recife, PE, Brazil., Lins MM; Paediatric Oncology Unit, Instituto de Medicina Integral Prof Fernando Figueira, Recife, PE, Brazil., Aguiar TF; Onco-Haematology Section, Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti, Rio de Janeiro, RJ, Brazil., Mansur MB; Biology of Childhood Leukaemia Team, Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK., Emerenciano M; Genetics of Acute Leukaemia Laboratory-GenLAb, Research and Innovation Coordination, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37, 6th floor, Rio de Janeiro, RJ 20231-050, Brazil. Electronic address: memerenciano@inca.gov.br.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2024 Dec; Vol. 50, pp. 102127. Date of Electronic Publication: 2024 Sep 22.
DOI:	10.1016/j.tranon.2024.102127
Abstrakt:	The presence of IKZF1 deletions has been associated with an increased relapse rate in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). There is a particular subset of IKZF1 del cases called IKZF1 plus (defined by the co-occurrence of IKZF1 del and deletions in CDKN2A/B, PAX5, or the PAR1 region, in the absence of ERG deletions), which is also associated with worse prognosis, but some recent studies have not found major differences between the IKZF1 del and IKZF1 plus groups. Therefore, the IKZF1 plus group still needs further comprehension and our study aims to characterise the molecular heterogeneity and identify molecular markers exclusively associated with IKZF1 plus . Two independent series of cases (TARGET, n = 125 and GenLAb, n = 60) were evaluated by segregating patients into 3 groups: IKZF1 plus , IKZF1 del , and IKZF1 wild . Differential expression analyses showed that the membrane protein-coding genes most associated with the IKZF1 plus group were: KCNA5, GREB1, EPOR, SDK1, and PTPRB. Notably, KCNA5 and GREB1 differential expression levels were validated in the GenLAb validation series. Regarding copy number alterations, we observed a high frequency of VPREB1 deletions in the IKZF1 plus group, as well as additional exclusive deletions in the CD200 and BTLA genes. Recent research suggests that the importance of the IKZF1 plus profile varies depending on the genetic subgroup. In this scenario, we found associations between IKZF1 plus and certain genes in BCP-ALL, being KCNA5 and GREB1 the most promising biomarkers for predicting IKZF1 plus . A deeper understanding of these genetic profiles will allow a better risk assessment and offer precise rationale for therapeutic strategies in BCP-ALL. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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