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

Abstract

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.

• Authors: Antonis Dagklis, Claudia Fazi, Cinzia Sala, Valeria Cantarelli, Cristina Scielzo, Roberto Massacane, Daniela Toniolo, Federico Caligaris-Cappio, Kostas Stamatopoulos, Paolo Ghia
• Journal: Blood (Blood) Vol. 114 Issue 1 Pg. 26-32 (Jul 02 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19029437 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complementarity Determining Regions

Topics

• 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, genetics, immunology)
• Lymphocyte Count
• Lymphocytosis (diagnosis, genetics, immunology)
• Male
• Middle Aged
• Mutation
• Pedigree
• Phenotype
• Preleukemia (diagnosis, genetics, immunology)
• Young Adult