PhD Scientific Days 2020

Pathology and Oncology III. Lectures

Pharmacogenetic Study of the Central Nervous System in Pediatric Acute Lymphoblastic Leukemia

Előadó neve

Dr. C. Sagi, Judit

Előadó munkahelye

Semmelweis University, Department of Genetics, Cell- and Immunobiology

Előadó telefonszáma

+36206632868

Előadó e-mail címe

sjudit08@gmail.com

Az előadás címe

Pharmacogenetic Study of the Central Nervous System in Pediatric Acute Lymphoblastic Leukemia

Szerző(k) neve és munkahelye

Judit C. Sagi 1*, Anna Artner 1, Andrea Kelemen 1, Balint Egyed 1, 2, Andrea Rzepiel 2, Nora Kutszegi 2,
Andras Gezsi 1, Gabor T. Kovács 2, Csaba Szalai 1, 3, Daniel J. Erdelyi 2, Agnes F. Semsei 1
1 Semmelweis University Department of Genetics, Cell- and Immunobiology, Budapest, Hungary,
2 Semmelweis University 2nd Department of Paediatrics, Budapest, Hungary,
3 Heim Pal Children Hospital, Budapest, Hungary

Szekció

Pathology and Oncology III. Lectures

Language of the presentation

English

Section, first choice

Pathology and Oncology

Section, second choice

Molecular Sciences

Összefoglaló szövege

Pediatric acute lymphoblastic leukemia (ALL) has a favorable prognosis thanks to the combined chemotherapy, however, relapsed disease and serious adverse effects caused by the treatment still need to take into consideration. We focused on the central nervous system (CNS) in pediatric ALL investigating ALL first relapse recurring in the CNS and the adverse effect, acute toxic encephalopathy (ATE). Interindividual differences regarding the diversity of symptoms connecting to CNS- relapse (REL) or neurotoxicity could be explained by the patients’ genetic background. We hypothesized single nucleotide polymorphisms (SNPs) can influence these events by modifying the function of enzymes and transporters which are located in the blood-brain-barrier and have a role in the metabolism of chemotherapeutic drugs. Clinical data were collected from the patients’ medical records retrospectively. ATE symptoms were graded according to the Common Terminology Criteria for Adverse Events v3.0. DNA was isolated from peripheral blood collected in remission (QIAmp® Blood DNA Maxi Kit, Qiagen). Genotyping was performed using TaqMan® OpenArray™ Genotyping System (Thermo Fisher Scientific). We studied the association between 62 SNPs and the incidence of CNS- REL or ATE. Logistic regression adjusted for potential confounders was performed using SPSS v25. Study population consisted of pediatric patients with ALL (0-18 years), 670 patients for ATE (cases= 86) and 842 for CNS- REL (cases= 30) projects, respectively. For the relapse project cases were isolated CNS- RELs or combined CNS and bone marrow RELs. We have found that the GSTP1 rs1695 G allele protected against ATE (p=0.002; OR=0.239; CI95%=0.096-0.597). Evaluating the association between these 62 SNPs and CNS- REL is still running. One GSTP1 variant associated with a reduced incidence of ATE. This result might contribute to personalized medicine in pediatric ALL: it could be a possible genetic marker for the risk of ATE after further investigations.
This study is supported by the ÚNKP-19-3-IV New National Excellence Program of the Ministry for Innovation and Technology; the National Research, Development and Innovation Office (NKFIH) Grants No. PD109200 (ÁF Semsei) and K115861 (DJ Erdélyi) and by the Hungarian Paediatric Oncology Network (07/MGYH-MGYGYT/2018).

Additional Information

Agnes F. Semsei
semsei.agnes@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1117

Start

16:30

End

16:45

Authors (legacy)

Judit C. Sagi 1*, Anna Artner 1, Andrea Kelemen 1, Balint Egyed 1, 2, Andrea Rzepiel 2, Nora Kutszegi 2,
Andras Gezsi 1, Gabor T. Kovács 2, Csaba Szalai 1, 3, Daniel J. Erdelyi 2, Agnes F. Semsei 1
1 Semmelweis University Department of Genetics, Cell- and Immunobiology, Budapest, Hungary,
2 Semmelweis University 2nd Department of Paediatrics, Budapest, Hungary,
3 Heim Pal Children Hospital, Budapest, Hungary