Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 4;60(1):38.
doi: 10.1007/s44313-025-00086-2.

SOX4 in chronic lymphocytic leukaemia: the forgotten transcription factor

Ricardo García-Muñoz  1 , Jone Alberdi-Ballina  2 , Giovanna Farfan-Quiroga  3 , Eloy F Robles  4 , María José Larráyoz  5 , María José Calasanz  5 , José Ángel Martínez-Climent  4 , Carlos Panizo  6 , Javier Larreina-Pérez  3 , Sofía Rincón-López  3 , Johelys Atencio-Matos  3 , Andrea Campeny-Najara  3 , Ada Esteban-Figuerola  3 , Montserrat Hernandez-Perez  3 , Puy Garrastachu-Zumaran  7 , María Velasco-Ruiz  7 , Estefanía Ruiz de Gaona  8 , Jesús Feliu  3
Affiliations

SOX4 in chronic lymphocytic leukaemia: the forgotten transcription factor

Ricardo García-Muñoz et al. Blood Res. .

Abstract

Purpose: SRY-box transcription factor 4 (SOX4) is a transcription factor involved in early B cell development and has been implicated in various malignancies; however, its role in chronic lymphocytic leukemia (CLL) remains poorly understood. This study investigated the correlation between SOX4 expression and prognostic factors in CLL to determine its relevance to disease progression and clinical outcomes.

Methods: A cohort of patients with CLL with a known immunoglobulin heavy chain variable region (IGHV) mutational status was analyzed for SOX4 expression using quantitative polymerase chain reaction (qPCR). Correlations between SOX4 levels and established prognostic markers including IGHV mutational status, cytogenetic abnormalities, and clinical outcomes were evaluated. Statistical analyses were performed to assess the association between SOX4 expression and patient survival.

Results: Higher SOX4 expression was observed to be significantly associated with unmutated CLL (U-CLL) and adverse prognostic markers, including del(17)(p13). In contrast, lower SOX4 levels were observed in mutated CLL (M-CLL), and cytogenetic abnormalities were noted to be linked to favorable outcomes [del(13)(q21)]. Survival analysis indicated that elevated SOX4 expression was correlated with poor prognosis.

Conclusion: SOX4 expression stratifies CLL subtypes and aligns with established prognostic markers. High SOX4 levels are associated with aggressive disease phenotypes, whereas low SOX4 expression is associated with better clinical outcomes. These findings indicate that SOX4 may serve as a potential biomarker for disease classification and risk stratification. Further studies are required to elucidate the biological significance of this phenomenon.

Keywords: Chronic Lymphocytic leukemia (CLL); Cytogenetic Abnormalities; IgHV mutational status; Prognostic Biomarkers; Risk Stratification; SOX4 expression.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
SOX4 gene expression according to the IGHV mutational status
Fig. 2
Fig. 2
Analysis of TTFT survival with high and low SOX4 gene expression. The graph shows the mean TTFT and highlights differences in treatment initiation timing between the groups, despite absence of statistically significant differences
Fig. 3
Fig. 3
SOX4 levels and their potential role in CLL development
See this image and copyright information in PMC

References

    1. Ghergus D, Martin M, Knapp AM, et al. Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation? Am J Hematol. 2024;99(1):48–56. 10.1002/ajh.27137. - PubMed
    1. García-Muñoz R, Llorente L. Chronic lymphocytic leukaemia: Could immunological tolerance mechanisms be the origin of lymphoid neoplasms? Immunology. 2014;142(4):536–50. 10.1111/imm.12285. - PMC - PubMed
    1. García-Muñoz R, Feliu J, Llorente L. The top ten clues to understand the origin of chronic lymphocytic leukemia (CLL). J Autoimmun. 2015;56:81–6. 10.1016/j.jaut.2014.10.005. - PubMed
    1. Kikushige Y, Ishikawa F, Miyamoto T, et al. Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell. 2011;20(2):246–59. 10.1016/j.ccr.2011.06.029. - PubMed
    1. Hadzidimitriou A, Darzentas N, Murray F, et al. Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia. Blood. 2009;113(2):403–11. 10.1182/blood-2008-07-166868. - PubMed

LinkOut - more resources