title: Immunogenetics shows that not all MBL are equal: the larger the clone, the more similar to CLL.
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 × 10(9)/L circulating clonal B cells. However, the clonal size in MBL is extremely variable and allows discrimination of two distinct entities (high-count [HC] and low-count [LC]-MBL) based on a cutoff value of 0.5 × 10(9)/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.
authors.affiliation: Hematology Department and Hematopoietic Cell Transplantation Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Vardi
authors.forename: Antonis
authors.initials: A
authors.lastname: Dagklis
authors.forename: Lydia
authors.initials: L
authors.lastname: Scarfò
authors.forename: Diane
authors.initials: D
authors.lastname: Jelinek
authors.forename: Darren
authors.initials: D
authors.lastname: Newton
authors.forename: Fiona
authors.initials: F
authors.lastname: Bennett
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Arancha
authors.initials: A
authors.lastname: Rodriguez-Caballero
authors.forename: Sallie
authors.initials: S
authors.lastname: Allgood
authors.forename: Mark
authors.initials: M
authors.lastname: Lanasa
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Ester
authors.initials: E
authors.lastname: Orlandi
authors.forename: Silvio
authors.initials: S
authors.lastname: Veronese
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Andy
authors.initials: A
authors.lastname: Rawstron
authors.forename: Tait
authors.initials: T
authors.lastname: Shanafelt
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D006801:Humans; D007125:Immunogenetics / Q000379:methods*; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000276:immunology* / Q000473:pathology; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D011947:Receptors, Antigen, B-Cell