Unit:
Library of the School of Health SciencesΠΜΣ Νεοπλασματική Νόσος στον Άνθρωπο: Έρευνα και Κλινικοπαθολογοανατομική Προσέγγιση στα Πλαίσια της Εξατομικευμένης Ιατρικής (Διάγνωση και Στοχευμένη Θεραπεία)
Author:
Fragioudaki Kleopatra
Supervisors info:
Ανδρέας Αγαθαγγελίδης, Επίκουρος Καθηγητής, Τμήμα Βιολογίας, ΕΚΠΑ
Σταμάτιος Θεοχάρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Σαμαρά, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, Πανεπιστήμιο Θεσσαλίας
Original Title:
Μελέτη των αναδιατάξεων των γονιδίων των ανοσοσφαιρινών σε ασθενείς με Χρόνια Λεμφοκυτταρική Λευχαιμία
Translated title:
Study of the clonotypic rearrangements of immunoglobulin genes in patients with Chronic Lymphocytic Leukemia
Summary:
Somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy chain variable gene (IGHV) is considered to be a critical biomarker for assessing the prognosis of patients with chronic lymphocytic leukemia (CLL). In this context, limited data is available for patients with more than one leukemic clone. To address this issue, we performed a comparative analysis of patients with monoclonal and oligoclonal CLL (m-CLL, o-CLL) at the immunogenetic level. We investigated the following immunogenetic characteristics: the IGHV/D/J gene expression repertoire, the CDR3 length and the SHM status.
The IGHV and IGHD gene repertoires showed a high degree of similarity between m-CLL and o-CLL, suggesting the existence of common antigenic stimuli in the two types of CLL. In contrast, the IGHJ gene repertoire exhibited a statistically different expression pattern among the two CLL types. The length of the CDR3 did not seem to be affected by the clonality pattern.
On the other hand, the SHM pattern of IGHV genes exhibited statistically significant differences between the two types of CLL, with the frequency of mutated rearrangements being significantly higher in o-CLL compared to m-CLL. In particular, the analysis of SΗM status in o-CLL, showed that a "concordant" SHM status (patients with only mutated, or only unmutated clones) was evident in the majority of cases, thus facilitating their prognosis. The subtypes with "concordant" mutated and "concordant" unmutated SΗM status displayed different patterns of IGHV gene expression, with different genes dominating the repertoire in each subtype. Finally, the expression of IGHV genes in the subtype with "discordant" SΗM (coexistence of mutated and unmutated clones) exhibited an intermediate pattern compared to the subgroups with "concordant" SΗM, suggesting the eventual prevalence of the unmutated clone over the mutated in such cases.
Main subject category:
Health Sciences
Keywords:
Chronic lymphocytic leukemia, Somatic hypermutation, Immunoglobulins, IGHV gene, Clonality pattern
