Immune thrombocytopenia in patients with chronic lymphocytic leukemia is associated with stereotyped B-cell receptors.
OBJECTIVE
To assess biologic features related to the development of immune thrombocytopenia (ITP) in patients with chronic lymphocytic leukemia (CLL).


METHODS
We retrospectively analyzed 463 patients with CLL with available immunoglobulin heavy-chain variable (IGHV) gene status and B-cell receptor (BCR) configuration [heavy-chain complementary-determining region 3 (HCDR3)], of whom thirty-six developed ITP, according to previously defined criteria. Most of them had available cytogenetic analysis.


RESULTS
We observed a significant association between ITP occurrence and IGHV unmutated gene status (P < 0.0001), unfavorable cytogenetic lesions (P = 0.005), and stereotyped HCDR3 (P = 0.006). The more frequent stereotyped HCDR3 subsets were #1 (IGHV1-5-7/IGHD6-19/IGHJ4; 16 of 16 unmutated) and #7 (IGHV1-69 or IGHV3-30/IGHD3-3/IGHJ6; 13 of 13 unmutated), both being significantly more represented among patients developing ITP (P = 0.003 and P = 0.001, respectively). Moreover, restricting the analysis to unmutated patients, subset #7 confirmed its independent significant association with the occurrence of ITP (P = 0.013). Both unmutated IGHV mutational status, del(11)(q23) and stereotyped BCR were significantly associated with shorter time to ITP development (P < 0.0001, P = 0.02, and P = 0.005, respectively) than other patients.


CONCLUSIONS
Our data suggest that patients with CLL and peculiar BCR conformations are at higher risk of developing secondary ITP and that stereotyped BCR may be involved in the pathogenesis of this complication.
Department of Hematology, Ospedale San Bortolo, Vicenza, Milano, Italy.
Carlo
C
Visco
Francesco
F
Maura
Giacomo
G
Tuana
Luca
L
Agnelli
Marta
M
Lionetti
Sonia
S
Fabris
Elisabetta
E
Novella
Ilaria
I
Giaretta
Gianluigi
G
Reda
Wilma
W
Barcellini
Luca
L
Baldini
Antonino
A
Neri
Francesco
F
Rodeghiero
Agostino
A
Cortelezzi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000706:statistics & numerical data; D012307:Risk Factors; D013921:Thrombocytopenia / Q000150:complications / Q000235:genetics / Q000276:immunology*
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell