Informace o publikaci

Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies

Název česky	Stereotypní B-buněčných receptorů v jedné třetině chronickou lymfocytární leukemií: molekulární klasifikace s důsledky pro cílených terapií
Autoři	AGATHANGELIDIS A. DARZENTAS Nikos HADZIDIMITRIOU A. BROCHET X. MURRAY F. YAN X. DAVIS Z. VAN GASTEL-MOL E. TRESOLDI C. CHU Ch. CAHILL N. GIUDICELLI V. TICHÝ Boris PEDERSEN L. FORONI L. BONELLO L. JANUS A. SMEDBY K. ANAGNOSTOPOULOS A. MERLE-BERAL H. LAOUTARIS N. JULIUSSON G. DI CELLE P. POSPÍŠILOVÁ Šárka JURLANDER J. GEISLER Ch. TSAFTARIS A. LEFRANC M. LANGERAK A. OSCIER D. CHIORAZZI N. BELESSI Ch. DAVI F. ROSENQUIST R. GHIA P. STAMATOPOULOS K.
Rok publikování	2012
Druh	Článek v odborném periodiku
Časopis / Zdroj	Blood
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
Doi	http://dx.doi.org/10.1182/blood-2011-11-393694
Obor	Onkologie a hematologie
Klíčová slova	HEAVY-CHAIN IIA; ANTIGEN RECEPTORS; APOPTOTIC CELLS; IMMUNOGLOBULIN; ANTIBODIES; IG; GENES; REPERTOIRE; SELECTION; SEQUENCE
Popis	Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset.