Molecular biomarkers in diagnosis, proceeding and therapeutic treatment in childhood haematologic malignancies

Doctoral Dissertation uoadl:2867548 121 Read counter

Τομέας Υγείας - Μητέρας - Παιδιού
Library of the School of Health Sciences
Deposit date:
Papadopoulou Anna
Dissertation committee:
Κωνσταντίνος Κωνσταντόπουλος, Καθηγητής, Ιατρική, ΕΚΠΑ
Παναγιώτης Παναγιωτίδης, Καθηγητής, Ιατρική, ΕΚΠΑ
Ελένη Φρυσίρα-Κανιούρα, Καθηγήτρια, Ιατρική ΕΚΠΑ
Θεόδωρος Π. Βασιλακόπουλος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Ευριδίκη Δρογκάρη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Αγγελοπούλου, Αναπληρώτρια Καθηγήτρια, Ιατρική ΕΚΠΑ
Μαρία Μοσχόβη, Επίκουρη Καθηγήτρια, Ιατρική ΕΚΠΑ
Original Title:
Μοριακοί δείκτες διάγνωσης, εξέλιξης και θεραπευτικής αντιμετώπισης παιδιών με αιματολογικές κακοήθειες
Translated title:
Molecular biomarkers in diagnosis, proceeding and therapeutic treatment in childhood haematologic malignancies
This report describes a newly-designed molecular method based on the high sensitive techniques Fragment analysis and Quantitative real-time PCR that is able to scan leukemic DNA at very low levels in the blood of patients with pediatric acute lymphoblastic leukemia.

Our study presents tracks of leukemic burden at diagnosis and on days 8, 15, 33 when the commonly used markers Bone marrow infiltration and Minimal Residual Disease (MRD) reduce the value (day 8) and eliminate it (days 15 and 33) giving the impression that blasts disappear from patient’s organism. Cell-free leukemic DNA can also be scanned on these days and appears to follow the same procession and behavior as nuclear leukemic DNA although at significantly lower levels.

The detection of blasts on days 15 and 33, when the number of white blood cells reduces significantly, is crucial for the progression and response to chemotherapy. The analysis of the methylation status of the promoter of Rassf6 gene reveals a methyl-CpG-domain that carries methylgroups the number of which differs between two major groups of patients. Those with favorable and those with unfavorable outcome. Therefore the detection of nuclear and cell-free leukemic DNA in blood circulation of patients with acute lymphoblastic leukemia using the hypermethylated promoter of Rassf6 gene adds prognostic value to minimal residual disease status and gives hope of potential marker in ALL to become as it follows the reduce of leukemic burden and the presence or absence of blasts in blood circulation during chemotherapy and for long time afterwards.
Main subject category:
Health Sciences
Acute lymphoblastic leukemia, Diagnosis, Molecular biomarker, Tumorsuppressor gene
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