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Determination of IGHV gene mutational status in chronic lymphocytic leukemia: bioinformatics advances meet clinical needs

Leukemia volume 22, pages 212–214 (2008)Cite this article

Over the past few years, the mutational status of the immunoglobulin heavy chain variable region (IGHV) genes has proved to be a major determinant in the prognostic evaluation of chronic lymphocytic leukemia (CLL).1 As this criterion becomes more frequently used for patient selection during clinical trials, its accurate determination is critical. In this regard, several technical recommendations have recently been proposed by an international panel of investigators, which should help to reach a better methodological standardization and obtain reliable sequences.

The correct determination of the mutational status strictly depends on the comparison of the nucleotide sequence of the clonal IGHV gene rearrangement expressed by the patient's leukemic cells with that of the closest germline counterpart. Although in theory this should be performed with the patient's germline DNA sequence from non-leukemic cells, it is a common practice to use public web-based databases, which provide a repository of the germline IGHV sequences along with various bioinformatic tools for sequence alignment. Several of these reference databases are available and include VBASE,2 GenBank/IgBLAST3 and the international ImMunoGeneTics information system® (IMGT).4 They differ in terms of the type of software employed, the criteria used to delineate the complementarity determining regions (CDR) and framework regions, as well as the extent of natural IGHV polymorphism taken into account. For all these reasons, discrepancies among the different databases occur when analyzing IGHV sequences, although it is not known to what extent they may affect the correct interpretation of the IGHV mutational status in CLL.

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Authors and Affiliations

  1. Laboratory of Hematology and University Pierre et Marie Curie, Hôpital Pitié-Salpètrière, Paris, France

    F Davi

  2. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

    R Rosenquist

  3. Department of Oncology, Università Vita-Salute San Raffaele e Istituto Scientifico San Raffaele, Milano, Italy

    P Ghia

  4. Department of Hematology, Nikea General Hospital, Athens, Greece

    C Belessi

  5. Department and HCT Unit, Hematology, G Papanicolaou Hospital, Thessaloniki, Greece

    K Stamatopoulos

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  1. F Davi
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  2. R Rosenquist
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  3. P Ghia
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  4. C Belessi
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  5. K Stamatopoulos
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Correspondence to F Davi.

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Davi, F., Rosenquist, R., Ghia, P. et al. Determination of IGHV gene mutational status in chronic lymphocytic leukemia: bioinformatics advances meet clinical needs. Leukemia 22, 212–214 (2008). https://doi.org/10.1038/sj.leu.2404969

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