title: B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia.
abstract: The development of autoimmune hemolytic anemia (AIHA) in patients with chronic lymphocytic leukemia (CLL) is associated with specific biological features. The occurrence of AIHA was hereby investigated in a retrospective series of 585 CLL patients with available immunoglobulin heavy chain variable (IGHV) gene status. AIHA occurred in 73 patients and was significantly associated with an IGHV unmutated (UM) status (P < 0.0001) and unfavorable [del(17)(p13) and del(11)(q23)] cytogenetic lesions (P < 0.0001). Stereotyped HCDR3 sequences were identified in 29.6% of cases and were similarly represented among patients developing or not AIHA; notably, subset #3 was associated with a significantly higher risk of AIHA than the other patients (P = 0.004). Multivariate analysis showed that UM IGHV, del(17)(p13) and del(11)(q23), but not stereotyped subset #3, were the strongest independent variables associated with AIHA. Based on these findings, we generated a biological risk score for AIHA development according to the presence of none (low risk), one (intermediated risk), or two (high risk) of the independent risk factors. Overall, our data indicate that UM IGHV status and/or unfavorable cytogenetic lesions are associated with the risk of developing secondary AIHA in CLL patients and suggest a possible role of specific stereotyped B-cell receptor subsets in a proportion of cases.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maura
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Erika
authors.initials: E
authors.lastname: Falisi
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Reda
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tuana
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Nicola
authors.initials: N
authors.lastname: Guercini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Novella
authors.forename: Ilaria
authors.initials: I
authors.lastname: Nichele
authors.forename: Anna
authors.initials: A
authors.lastname: Montaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Autore
authors.forename: Anna
authors.initials: A
authors.lastname: Gregorini
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Mauro
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology / Q000235:genetics*; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell