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Abstract
In an optimized management algorithm of chronic lymphocytic leukemia (CLL), the early identification of high-risk patients, ideally prior to treatment, is a prerequisite for designing strategies tailored at overcoming therapy resistance. TP53 abnormalities play a central role in our current understanding of the poor prognosis of high-risk CLL patients, but fail to explain the molecular basis of 50% of high-risk CLL. Next-generation sequencing studies have revealed several novel genetic alterations in high-risk CLL, including NOTCH1, SF3B1 and BIRC3 mutations. Alterations of these genes occur in 5–10% of CLL at diagnosis, show a prevalence that increases in the more advanced phases of the disease, and confer poor prognosis in consecutive CLL series.
Financial & competing interests disclosure
Work by the authors described in this review was supported by AIRC, Special Program Molecular Clinical Oncology, 5 x 1000, No. 10007, Milan, Italy (to G Gaidano); Progetto FIRB-Programma ‘Futuro in Ricerca’ 2008 (to D Rossi), PRIN 2008 (to G Gaidano) and PRIN 2009 (to D Rossi), MIUR, Rome, Italy; Progetto Giovani Ricercatori 2008 (to D Rossi), Progetto Giovani Ricercatori 2010 (to D Rossi), Ricerca Sanitaria Finalizzata 2008 and 2009 (to G Gaidano), Ministero della Salute, Rome, Italy; and Novara-AIL Onlus, Novara, Italy (to G Gaidano). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.