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Are surrogates of IGHV gene mutational status useful in B-cell chronic lymphocytic leukemia? The example of Septin-10

Leukemia volume 22, pages 224–226 (2008)Cite this article

We read with interest the study by Bilban et al.,1 which compared the gene expression profile (GEP) of two groups of B-cell chronic lymphocytic leukemia (CLL), selected for different lipoprotein lipase (LPL) mRNA levels. Several GEP studies have shown that LPL, an essential enzyme of lipid metabolism, is one of the genes most closely associated with unmutated (UM) immunoglobulin variable heavy chain (IGHV) genes in CLL. On these basis, LPL has been proposed as a novel predictor for overall survival and progression in CLL patients.2 Among 111 genes differentially expressed by CLL with high or low LPL expression, Bilban et al.1 documented that expression of Septin-10 (SEPT10) significantly correlates with both high LPL mRNA levels and UM IGHV gene status. The authors highlighted also the prognostic value of SEPT10 as a time-to-treatment predictor, with a significant earlier need for therapy occurring in patients with high SEPT10 mRNA levels.1

We recently reported a comprehensive characterization of IGHV3-21-expressing CLL, a disease subset recognized as a specific poor prognosis category, given its clinical behavior mostly independent of IGHV gene mutation status.3 In this respect, we and others have demonstrated that IGHV3-21 CLL, although frequently displaying a mutated (M) IGHV gene configuration, has an overall survival similar to poor-prognosis UM CLL.3, 4, 5 Consistently, GEP studies performed by our group and comparison of IGHV3-21 CLL versus non-IGHV3-21 CLL have identified a restricted number of genes (122 probes corresponding to 115 genes) whose differential expression may explain, at least in part, the clinical aggressiveness of IGHV3-21 CLL.3 By reviewing the list of the 122 probes differentially expressed by IGHV3-21 CLL,1 we found SEPT10 among the 62 probes (59 genes) significantly downregulated in this CLL subset.3 Downregulation of SEPT10 in IGHV3-21 CLL was an unexpected finding, because SEPT10 expression is considered a poor prognostic marker and IGHV3-21 CLL typically has poor clinical outcome.

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References

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Acknowledgements

This work was supported in part by Ministero della Salute (Ricerca Finalizzata IRCCS and ‘Alleanza Contro il Cancro’), Rome; Programmi di Ricerca di Interesse Nazionale (PRIN) and Fondo per gli Investimenti per la Ricerca di Base (FIRB), MUR, Rome; Associazione Italiana contro le Leucemie linfomi e mielomi (AIL)—Venezia, Pramaggiore group (fellowship to MDB); Novara-AIL Onlus, Novara; Ricerca Scientifica Applicata Regione Piemonte, Torino.

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Authors and Affiliations

  1. Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy

    D Benedetti, R Bomben, M Dal-Bo, A Zucchetto, M Degan & V Gattei

  2. Department of Physics, University of Bologna, Bologna, Italy

    D Marconi

  3. Division of Hematology and Transplant, Department of Clinical Medicine and Immunological Sciences, University of Siena, Siena, Italy

    F Forconi

  4. Hematology section, S Eugenio Hospital, University of Tor Vergata, Rome, Italy

    G Del-Poeta

  5. Division of Hematology, Department of Clinical and Experimental Medicine and Interdisciplinary Research Center on Autoimmune Diseases (IRCAD), Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    G Gaidano

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  1. D Benedetti
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Correspondence to V Gattei.

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Benedetti, D., Bomben, R., Dal-Bo, M. et al. Are surrogates of IGHV gene mutational status useful in B-cell chronic lymphocytic leukemia? The example of Septin-10. Leukemia 22, 224–226 (2008). https://doi.org/10.1038/sj.leu.2404867

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