PhD Scientific Days 2020

Pathology and Oncology I. Posters

Retrospective Analysis of Genetic Markers with Prognostic Significance in Chronic Lymphocytic Leukemia

Előadó neve

Dr. Aczél, Dóra

Előadó munkahelye

1st Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

+36204365149

Előadó e-mail címe

aczel.dora@med.semmelweis-univ.hu

Az előadás címe

Retrospective Analysis of Genetic Markers with Prognostic Significance in Chronic Lymphocytic Leukemia

Szerző(k) neve és munkahelye

Dóra Aczél1, Donát Alpár2

1 MTA-SE Momentum Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 MTA-SE Momentum Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest

Szekció

Pathology and Oncology I. Posters

Language of the presentation

Hungarian

Section, first choice

Pathology and Oncology

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction: Previous studies of chronic lymphocytic leukemia (CLL) suggested that genetic biomarkers such as chromosome abnormalities, TP53 mutations and mutational status of the immunoglobulin heavy-chain variable (IGHV) gene are associated with prognosis and can stratify patients for standard chemo-immunotherapy or for novel targeted therapies.
Aims: To investigate the distribution and prognostic significance of recurrent genetic alterations in a large cohort of Hungarian CLL patients.
Methods: Diagnostic peripheral blood samples from 1509 patients were collected in the 1st Department of Pathology and Experimental Cancer Research, Semmelweis University. Trisomy of chromosome 12 as well as deletions of the chromosome regions 11q (ATM), 13q (DLEU) and 17p (TP53) were screened by fluorescence in situ hybridization. Coding region of the TP53 gene was interrogated by Sanger and/or next-generation sequencing (NGS). IGHV mutational status was analyzed by Sanger sequencing, with the results being interpreted according to the recommendations of the European Research Initiative on CLL (ERIC).
Results: Trisomy 12 proved to be most common cytogenetic abnormality (28%), while deletions including del(11q), del(13q) and del(17p) were observed in 22.0%, 18.5% and 6.8% of the patients, respectively. Del(13q) was associated with the longest median time-to-first treatment period, while del(11q) and del(17p) were associated with more advanced disease stage. TP53 mutations were identified in 11% of the cases; these patients are typically resistant to standard chemo-immunotherapy but can greatly benefit from novel targeted therapies. Forty percent of all analyzed cases showed a mutated IGHV pattern usually associated with longer survival, while unmutated IGHV status typically being correlated with more adverse clinical outcome was observed in 54% of the patients. In 10% of the cases, prognostic IGHV receptor stereotypes were detected, from which 2.4% belonged to the so called group #2, associated with very poor prognosis.
Conclusions: In our cohort, distribution of recurrent genetic markers showed high concordance with data previously reported by large international studies. The results confirm that molecular cytogenetic and molecular genetic alterations can serve as reliable biomarkers for prognosis assessment and treatment response prediction in CLL.

Additional Information

Doctoral School: Pathology
Program: Oncology
Supervisor: Donát Alpár
E-mail address: alpar.donat@med.semmelweis-univ.hu

ÚNKP: ÚNKP-19-3-I-SE-33

Supporting grants: NKFIH K16-119950; KH17-126718 and NVKP_16-1-2016-0004; ÚNKP-19-3-I-SE-33; ÚNKP-19-4-SE-77; HAS LP95021; STIA_18_KF; János Bolyai Scholarship Program; EFOP-3.6.3-VEKOP-16-2017-00009

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4161

Start

11:26

End

11:29

Authors (legacy)

Dóra Aczél1, Donát Alpár2

1 MTA-SE Momentum Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 MTA-SE Momentum Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest