The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring

Blood. 2009 Jul 2;114(1):26-32. doi: 10.1182/blood-2008-09-176933. Epub 2008 Nov 24.


In the revised National Cancer Institute Working Group (NCI-WG)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for CLL, CLL-like monoclonal B lymphocytosis (MBL) is defined as the presence of less than 5 x 10(9)/L B lymphocytes in the peripheral blood. However, the concentration of MBL in the blood is extremely variable. MBL in subjects with lymphocytosis require treatment at a rate of 1.1% per year and present immunoglobulin (IG) gene features and similar to good prognosis CLL. Little is known about low-count MBL cases, accidentally found in the general population. We analyzed IGHV-D-J rearrangements in 51 CLL-like MBL cases from healthy individuals, characterized by few clonal B cells. Seventy percent of the IGHV genes were mutated. The most frequent IGHV gene was IGHV4-59/61, rarely used in CLL, whereas the IGHV1-69 gene was lacking and the IGHV4-34 gene was infrequent. Only 2 of 51 (3.9%) MBL cases expressed a CLL-specific stereotyped HCDR3. Therefore, the IG gene repertoire in low-count MBL differs from both mutated and unmutated CLL, suggesting that the detection of MBL in an otherwise healthy subject is not always equivalent to a preleukemic state. Detailed IG analysis of individual MBL may help to identify cases that necessitate continuous clinical monitoring to anticipate disease progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / immunology*
  • Complementarity Determining Regions
  • Diagnosis, Differential
  • Female
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin*
  • Humans
  • Italy
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymphocyte Count
  • Lymphocytosis / diagnosis
  • Lymphocytosis / genetics*
  • Lymphocytosis / immunology*
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Phenotype
  • Preleukemia / diagnosis
  • Preleukemia / genetics
  • Preleukemia / immunology
  • Young Adult


  • Complementarity Determining Regions