title: 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.affiliation: Department of Oncology, Università Vita-Salute San Raffaele, Milano, Italy.
authors.forename: Antonis
authors.initials: A
authors.lastname: Dagklis
authors.forename: Claudia
authors.initials: C
authors.lastname: Fazi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sala
authors.forename: Valeria
authors.initials: V
authors.lastname: Cantarelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Scielzo
authors.forename: Roberto
authors.initials: R
authors.lastname: Massacane
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions; D003937:Diagnosis, Differential; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007558:Italy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011289:Preleukemia / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D022801:Complementarity Determining Regions