Immunogenetics shows that not all MBL are equal: The larger the clone, the more similar to CLL

Anna Vardi, Antonis Dagklis, Lydia Scarfo, Diane Jelinek, Darren Newton, Fiona Bennett, Julia Almeida, Arancha Rodriguez-Caballero, Sallie Allgood, Mark Lanasa, Agostino Cortelezzi, Ester Orlandi, Silvio Veronese, Marco Montillo, Andy Rawstron, Tait Shanafelt, Alberto Orfao, Kostas Stamatopoulos, Paolo Ghia

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Chronic lymphocytic leukemia (CLL) -like monoclonal B-cell lymphocytosis (MBL) shares common immunophenotype and cytogenetic abnormalities with CLL, from which it is discriminated by a cutoff value of 5 3 109/L circulating clonal B cells. However, the clonal size in MBL is extremely variable and allows discrimination of two distinct entities (highcount [HC] and low-count [LC]-MBL) based on a cutoff value of 0.5 3 109/L clonal B cells. HC-MBL is associated with lymphocytosis and progresses to CLL requiring treatment at a rate of 1.1% per year, whereas LC-MBL is found in the general population only through high-sensitivity techniques and carries limited, if any, risk of progression.We performed an immunogenetic profiling of 333 cases with CLL-like MBL supplemented by detailed comparisons with CLL, focusing especially on CLL Rai stage 0 (CLL-0). LC- and HC-MBL had similar somatic hypermutation status, yet different IGHV gene repertoires and frequencies of B-cell receptor (BcR) stereotypy. In particular, stereotyped BcRs were infrequent in LC-MBL and were often not CLL specific. In contrast, HC-MBL exhibited clear immunogenetic similarities to CLL-0. These findings indicate that LC-MBL may not represent a true preleukemic condition, thus differing from HC-MBL/CLL-0 in which the identification of factors endowing malignant potential is strongly warranted.

Original languageEnglish (US)
Pages (from-to)4521-4528
Number of pages8
JournalBlood
Volume121
Issue number22
DOIs
StatePublished - May 30 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Vardi, A., Dagklis, A., Scarfo, L., Jelinek, D., Newton, D., Bennett, F., Almeida, J., Rodriguez-Caballero, A., Allgood, S., Lanasa, M., Cortelezzi, A., Orlandi, E., Veronese, S., Montillo, M., Rawstron, A., Shanafelt, T., Orfao, A., Stamatopoulos, K., & Ghia, P. (2013). Immunogenetics shows that not all MBL are equal: The larger the clone, the more similar to CLL. Blood, 121(22), 4521-4528. https://doi.org/10.1182/blood-2012-12-471698