Evidence map›Paper›PMID 42823720›Full record

ArticleBiomarker research2026

ZNF292 mutations impair RNA and protein biosynthesis defining an adverse prognostic subset in early-stage chronic lymphocytic leukemia.

Alberto Rodríguez-Sánchez, María Alonso-Gago, Claudia Pérez-Carretero, Luis A Corchete-Sánchez, Cristina Miguel-García, Sandra Santos-Minguez, Ángela Villaverde-Ramiro, José Antonio Queizán-Hernandez, Araceli Rubio, Rocío Benito-Sánchez and 6 more

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Article in Biomarker research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Alberto Rodríguez-SánchezCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
María Alonso-GagoCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
Claudia Pérez-CarreteroCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
Luis A Corchete-SánchezMassachusetts General Hospital Center for Cancer Research, Charlestown, MA, 02129, USA.
Cristina Miguel-GarcíaCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
Sandra Santos-MinguezCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
Ángela Villaverde-RamiroCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
José Antonio Queizán-HernandezDepartment of Hematology, Hospital de Segovia, Segovia, Spain.
Araceli RubioDepartment of Hematology, Hospital Miguel Servet, Zaragoza, Spain.
Rocío Benito-SánchezCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
Federico Lo SchiavoBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
Martina GhettiBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
Giorgia SimonettiBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
Ana E Rodríguez-VicenteCancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain. anita82@usal.es.
Jesús M Hernández-Rivas *Cancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain.
Miguel Quijada-Álamo *Cancer Research Center, University of Salamanca, IBSAL, IBMCC, CSIC, Salamanca, Spain. miguel.quijada-lamo@mssm.edu.

Funding

Consejería de Educación, Junta de Castilla y León EDU/1868/2022Instituto de Salud Carlos III PI24/01432
6 · The paper itself

Abstract

backgroundZNF292 alterations are recurrently detected in patients with chronic lymphocytic leukemia (CLL), occurring in 3%-6% of patients as mutations and in 2% as 6q deletions. Although preliminary evidence suggested an independent prognostic role for ZNF292 mutations, their specific clinical relevance in early-stage CLL and the underlying biological mechanisms remain poorly defined.

methods488 CLL patients were analyzed using targeted Next-Generation Sequencing (NGS) to characterize the landscape and clinical significance of ZNF292 mutations. CRISPR/Cas9-genome editing was employed to introduce the most prevalent ZNF292 variants into CLL cellular models. Their biological and functional implications were evaluated by integrating RNA-sequencing data from these isogenic cellular models with transcriptomic data from primary patient samples, complemented by functional validation and drug response assays.

resultsZNF292 mutations were associated with shorter time to first treatment (TTFT; median 25 vs. 52 months, P = 0.009) and inferior overall survival (OS, median 93 vs. 148 months, P = 0.004). Importantly, when restricting the analyses to early-stage cases, ZNF292 alterations were independently associated with shorter TTFT and OS, identifying a high-risk subgroup. Mechanistically, transcriptomic analyses revealed that ZNF292 mutations suppress global protein biosynthesis and modulate cell cycle progression in both primary CLL samples and CRISPR/Cas9-edited cells. Furthermore, ZNF292 deficiency impaired replication stress responses via defective CHK1 activation, resulting in DNA damage accumulation. Evaluating potential therapeutic vulnerabilities, ZNF292-mutated cells exhibited enhanced in vitro sensitivity to ibrutinib and venetoclax.

conclusionsOur findings propose ZNF292 alterations as an independent prognostic factor in early-stage CLL and unveil their role in disease progression.

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.