TY - JOUR
T1 - B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia
AU - Maura, Francesco
AU - Visco, Carlo
AU - Falisi, Erika
AU - Reda, Gianluigi
AU - Fabris, Sonia
AU - Agnelli, Luca
AU - Tuana, Giacomo
AU - Lionetti, Marta
AU - Guercini, Nicola
AU - Novella, Elisabetta
AU - Nichele, Ilaria
AU - Montaldi, Anna
AU - Autore, Francesco
AU - Gregorini, Anna
AU - Barcellini, Wilma
AU - Callea, Vincenzo
AU - Mauro, Francesca R.
AU - Laurenti, Luca
AU - Foà, Robin
AU - Neri, Antonino
AU - Rodeghiero, Francesco
AU - Cortelezzi, Agostino
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.23342
DO - 10.1002/ajh.23342
M3 - Article
C2 - 23115077
AN - SCOPUS:84871404373
VL - 88
SP - 32
EP - 36
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 1
ER -