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Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

ABSTRACT: Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0-2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.

SUBMITTER: Suarez-Cabrera A

PROVIDER: S-EPMC9394282 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

Suárez-Cabrera Alexia A Fiallo-Suárez Dolly Viviana DV Stuckey Ruth R Uroz-de la Iglesia Marta Luna ML Florido Yanira Y Lemes-Castellano Angelina A Perera-Álvarez Miguel Ángel MÁ Luzardo-Henríquez Hugo H de la Nuez Haridian H Fernández-Caldas Paula P de la Iglesia Silvia S Gómez-Casares María Teresa MT Bilbao-Sieyro Cristina C

Diagnostics (Basel, Switzerland) 20220725 8

Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, <i>TP53</i> mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to firs ...[more]

PMID: 35892513

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Project description:Chronic lymphocytic leukemia (CLL) presents with heterogeneous clinical outcomes, suggesting varied underlying pathogenic mechanisms. This study aims to elucidate the impact of T follicular helper (Tfh) cells on CLL progression and prognosis. Gene expression profile data for CLL were collected from GSE22762 and GSE39671 datasets. Patients were divided into high and low groups using Tfh levels using the optimal cutoff value based on overall survival (OS) and time-to-first treatment (TTFT). Differential expression analysis was performed between these groups, followed by co-expression network analysis and single-sample Gene Set Enrichment Analysis (ssGSEA). Marker genes of Tfh cells were used to construct prognostic models. Additionally, 40 CLL patients were recruited and categorized based on median Tfh levels. Marker gene expression was assessed using RT-qPCR and Western Blot, and immune cell levels were determined through flow cytometry. The high group showed better prognosis compared to the low group. Among the 1121 differentially expressed genes identified, five co-expression networks were constructed, with the turquoise module showing the highest correlation with Tfh cells. Genes within this module significantly participate in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and natural killer cell mediated cytotoxicity. Tfh cells were significantly negatively correlated with activated B cells and positively correlated with Tregs. The Random Survival Forest (RSF) model identified 10 marker genes, and further analysis using Lasso regression and nomogram selected CLEC4A, RAE1, CD84, and PRDX1 as prognostic markers. In the high group, levels of CLEC4A and RAE1 were higher than in the low group, whereas CD84 and PRDX1 were lower. Flow cytometry revealed that the level of activated B cells in the high Tfh group was significantly lower than in the low Tfh group, while the level of Tregs is significantly higher in the high Tfh group. This study seeks to contribute to a more detailed understanding of the pathogenesis of CLL, delving into the prognostic significance of Tfh.

Dataset Information

Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

Publications

Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

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