Clinical implications of DNA damage repair in acute myeloid leukaemia

Overview

Project Summary

Although hematological malignancies form a small fraction of new cancer diagnoses, the increasing life expectancy in the Western world foresees a rise in Acute Myeloblastic Leukemia (AML) cases. Recent studies suggest that genomic instability, chromosomal abnormalities, and gene mutations in AML may result from alterations in the DNA Damage Response/Repair (DDR) pathway, raising unanswered questions. Establishing a DNA repair activity signature could identify prognostic biomarkers namely for high-risk cytogenetically normal AML (CN-AML) patients, guiding optimal treatment and improving outcomes. Understanding DDR abnormalities is crucial for CN-AML comprehension and enhanced clinical care quality.

Main Goals

Our main goal is to assess the association between DDR and CN-AML, and the impact in classification, risk stratification, progression, and therapy response. Additionally, we aim to exploit the synthetic lethal interactions between DDR inhibitors combined with each other and with standard chemotherapy in AML and identify a DNA repair signature/phenotype, based on a gene expression profile, in order to define a repair activity score, and/or a genomic instability pattern, that help to select the best treatment approach. 

Project Details