Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

Panagiotis Baliakas, Andreas Agathangelidis, Anastasia Hadzidimitriou, Lesley-Ann Sutton, Eva Minga, Athina Tsanousa, Lydia Scarfò, Zadie Davis, Xiao-Jie Yan, Tait Shanafelt, Karla Plevova, Yorick Sandberg, Fie Juhl Vojdeman, Myriam Boudjogra, Tatiana Tzenou, Maria Chatzouli, Charles C Chu, Silvio Veronese, Anne Gardiner, Larry MansouriKarin E Smedby, Lone Bredo Pedersen, Denis Moreno, Kirsten Van Lom, Véronique Giudicelli, Hana Skuhrova Francova, Florence Nguyen-Khac, Panagiotis Panagiotidis, Gunnar Juliusson, Lefteris Angelis, Achilles Anagnostopoulos, Marie-Paule Lefranc, Monica Facco, Livio Trentin, Mark Catherwood, Marco Montillo, Christian H Geisler, Anton W Langerak, Sarka Pospisilova, Nicholas Chiorazzi, David Oscier, Diane F Jelinek, Nikos Darzentas, Chrysoula Belessi, Frederic Davi, Paolo Ghia, Richard Rosenquist, Kostas Stamatopoulos

    68 Citations (Scopus)

    Abstract

    An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

    Original languageEnglish
    JournalBlood
    Volume125
    Issue number5
    Pages (from-to)856-9
    Number of pages4
    ISSN0006-4971
    DOIs
    Publication statusPublished - 29 Jan 2015

    Keywords

    • Aged
    • Antineoplastic Agents
    • B-Lymphocytes
    • Female
    • Gene Expression Regulation, Leukemic
    • Gene Rearrangement, B-Lymphocyte, Heavy Chain
    • Genetic Heterogeneity
    • Humans
    • Immunoglobulin Heavy Chains
    • Leukemia, Lymphocytic, Chronic, B-Cell
    • Male
    • Middle Aged
    • Prognosis
    • Somatic Hypermutation, Immunoglobulin
    • Survival Analysis
    • Time-to-Treatment
    • Treatment Outcome

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