Stereotipija B-ćelijskog receptora u hroničnoj limfocitnoj leukemiji

Abstract

Opsežne imunogenetičke studije sprovedene tokom proteklih nekoliko decenija u oblasti hronične limfocitne leukemije (HLL) su identifikovale grupe pacijenata koji eksprimiraju visoko homologne, skoro identične imunoglobulinske molekule koji ulaze u sastav B-ćelijskog receptora (BĆR IG). Ovaj fenomen, nazvan „BĆR stereotipija“, obuhvata oko 30% HLL i predstavlja najvažniju potvrdu uloge antigenske stimulacije u patogenezi i evoluciji bolesti. Na osnovu sekvence CDR3 regiona teških lanaca IG definisani su stereotipni subsetovi koji ispoljavaju konzistentne subset-specifične biološke i kliničke karakteristike. Neki od najzastupljenijih subsetova imaju i jasan prognostički značaj, tako da se čak mogu smatrati različitim varijantama bolesti. Subklasifikacija HLL bazirana na BĆR stereotipiji je omogućila kompartmentalizovan pristup u istraživanju ove bolesti, i otvorila mogućnost za precizniju stratifikaciju pacijenata, kao i uspešniju prognostiku i lečenje, uprkos izrazitoj kliničkoj heterogenosti HLL.

During the past several decades, extensive immunogenetic research of chronic lymphocytic leukemia (CLL) led to the identification of groups of patients expressing highly homologous, almost identical B-cell receptor immunoglobulin molecules (BCR IG). This phenomenon, termed „BCR stereotypy“, accounts for around 30% of all CLL and represents the strongest evidence for the role of antigenic stimulation in CLL pathogenesis and evolution. Based on the sequence of CDR3 region within IG heavy chains multiple stereotyped subsets have been defined, which display consistent subset-specific biological and clinical characteristics. Some of the most frequent subsets also exert strong prognostic significance and can be considered to be distinct disease variants. Stereotypy-based CLL subclassification enabled compartmentalized approach in the research of this disease, and offered the possibility of refining stratification of patients that can improve prognostication and clinical decision-making despite extreme heterogeneity of CLL.