Investigating novel prognostic groups in MDS and AML identified using the DNA damage repair deficiency gene signature

Survival analyses revealed that the DDRD signature is a prognostic tool for AML patients and for MDS patients under 65 years old or have the intermediate-2 risk classification. Differential gene expression analyses revealed immune signalling pathways to be driving the DDRD phenotype in MDS and AML.

Expression of two genes from the DDRD signature, MX1 and IFI44L, were found to be independent prognostic biomarkers for AML. MDS and AML in vitro cell models were classified using the DDRD signature and experiments did not uncover a DNA repair defect associated with the DDRD signature classification. Further bioinformatic analyses across multiple AML datasets revealed IFNγ signalling to consistently be the top enriched hallmark in the DDRD+ patient cohort.