<i>CAT</i> rs1001179 Single Nucleotide Polymorphism Identifies an Aggressive Clinical Behavior in Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is characterized by an extremely variable clinical course. Although several parameters have been shown to be associated with clinical outcomes in patients with CLL, there remains substantial intragroup clinical heterogeneity in otherwise molecularly and staging homogeneous CLL subgroups. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course and that higher CAT expression is associated with the presence of the rs1001179 single nucleotide polymorphism (SNP) T allele in the CAT promoter. Herein, we genotyped CLL patients for CAT rs1001179 SNP in an exploratory study (n = 235) and in a sequential independent validation study (n = 531). Time-to-event modeling analyses for time-to-first-treatment (TTFT) from the two patients' cohorts showed that TT genotype was associated with a shorter TTFT, independently of other currently used prognostic parameters in CLL. Moreover, the TT genotype identifies CLL patients with a faster clinical progression even within subgroups of patients with low-risk biological and clinical hallmarks. In conclusion, our data show that the TT genotype identifies CLL patients with a shorter TTFT, pointing to this SNP as a possible prognostic factor, which can improve patients' risk stratification leading to better patient management and personalized therapeutic choices.
Authors
- Simona Gambino (ORCID: https://orcid.org/0000-0003-1530-0148)
- Omar Perbellini (ORCID: https://orcid.org/0000-0002-8278-8916)
- Marilisa Galasso (ORCID: https://orcid.org/0000-0003-3028-1205)
- Isacco Ferrarini (ORCID: https://orcid.org/0000-0001-9867-8335)
- Mauro Krampera (ORCID: https://orcid.org/0000-0002-7280-2040)
- Riccardo Moia (ORCID: https://orcid.org/0000-0001-7393-1138)
- Ester Lovato
- Ornella Lovato
- Carlo Visco (ORCID: https://orcid.org/0000-0003-2863-0883)
- Gianluca Gaïdano (ORCID: https://orcid.org/0000-0002-4681-0151)
- Maria Teresa Scupoli (ORCID: https://orcid.org/0000-0002-3352-7859)
- Massimo Donadelli (ORCID: https://orcid.org/0000-0001-9224-9230)
- Francesca Maria Quaglia (ORCID: https://orcid.org/0000-0003-4347-3775)
- Chiara Cosentino (ORCID: https://orcid.org/0000-0003-1324-4007)
- Valentina Mozzo (ORCID: https://orcid.org/0000-0003-3794-0445)
- Maria Elena Carazzolo (ORCID: https://orcid.org/0009-0008-2742-2779)
- Maria Romanelli
- Vittoria Salaorni (ORCID: https://orcid.org/0009-0006-2941-3804)
Institutions
- University of Verona (IT)
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- AULSS 2 Marca Trevigiana (IT)
- Istituto Oncologico Veneto (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Publication Details
- Journal
- Hematological Oncology
- Published
- 2024-11-01
- DOI
- https://doi.org/10.1002/hon.70002
- Citations
- 1
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.44
Funders
- European Commission
- Associazione Italiana per la Ricerca sul Cancro
- Università degli Studi di Verona