Molecular Evidence for Antigen Drive in the Natural History of Mantle Cell Lymphoma

Varování

Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	XOCHELLI Aliki SUTTON Lesley-Ann AGATHANGELIDIS Andreas STALIKA Evangelia KARYPIDOU Maria MARANTIDOU Fotini LOPEZ Alba Navarro PAPADOPOULOS Giorgos ŠUPÍKOVÁ Jana GROENEN Patricia BOUDJOGRA Myriam SUNDSTROM Christer PONZONI Maurilio SKUHROVÁ FRANCOVÁ Hana ANAGNOSTOPOULOS Achilles POSPÍŠILOVÁ Šárka PAPADAKI Theodora TZOVARAS Dimitris GHIA Paolo POTT Christiane DAVI Frederic CAMPO Elias ROSENQUIST Richard HADZIDIMITRIOU Anastasia BELESSI Chrysoula STAMATOPOULOS Kostas
Rok publikování	2015
Druh	Článek v odborném periodiku
Časopis / Zdroj	AMERICAN JOURNAL OF PATHOLOGY
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.sciencedirect.com/science/article/pii/S0002944015001388
Doi	http://dx.doi.org/10.1016/j.ajpath.2015.02.006
Obor	Onkologie a hematologie
Klíčová slova	CHRONIC LYMPHOCYTIC-LEUKEMIA; INDUCED CYTIDINE DEAMINASE; V-H GENES; CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; B-CELLS; IMMUNOGLOBULIN RECEPTORS; CLONAL EVOLUTION; SPLICE VARIANTS; MUTATION STATUS
Přiložené soubory	ZVV_2015_116_1318372_Molecular_Evidence.pdf
Popis	To further our understanding about antigen involvement in mantle cell Lymphoma (MCL), we analyzed the expression levels of activation-induced cytidine deaminase (AID), a key player in B-cell responses to antigen triggering, in 133 MCL cases; assessed the functionality of AID by evaluating in vivo class switch recombination in 52 MCL cases; and sought for indications of ongoing antigen interactions by exploring intraclonal diversification within 14 MCL cases. The AID full-length transcript and the most frequent splice variants (AID-Delta E4a, AID-Delta E) were detected in 128 (96.2%), 96 (72.2%), and 130 cases (97.7%), respectively. Higher AID full-Length transcript levels were significantly associated (P < 0.001) with Lack of somatic hypermutation within the clonotypic immunoglobulin heavy variable (IGHV) genes. Median AID transcript levels were higher in lymph node material compared to cases in which peripheral blood was analyzed, implying that clonal behavior is influenced by the microenvironment. Switched tumor-derived IGHV-IGHD-IGHJ transcripts were identified in 5 of 52 cases (9.6%), all of which displayed somatic hypermutation and AID-mRNA expression. Finally, although most cases exhibited low levels of intraclonal diversification, analysis of the mutational activity revealed a precise targeting of somatic hypermutation indicative of an active, ongoing interaction with antigen(s). Collectively, these findings strongly allude to antigen involvement in the natural history of MCL, further challenging the notion of antigen naivety.
Související projekty:	CEITEC - středoevropský technologický institut Molekulární charakterizace B buněčných receptorů a jejich vztah k evoluci genetických změn u chronické lymfocytární leukémie Expression and function of activation-induced cytidine deaminase splice variants in normal B cell physiology and chronic lymphocytic leukemia