The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome.
Marius KülpPatrizia LargheroJulia AltenGunnar CarioCornelia EckertAurélie Caye-EudeHélène CaveTessa SchmachtelMichela BardiniGiovanni CazzanigaPaola De LorenzoMaria Grazia ValsecchiHalvard BonigClaus MeyerMichael A RiegerRolf MarschalekPublished in: Leukemia (2023)
KMT2A-rearranged acute lymphoblastic infant leukemia (KMT2A-r iALL) is associated with outsize risk of relapse and relapse mortality. We previously reported strong upregulation of the immediate early gene EGR3 in KMT2A::AFF1 iALL at relapse; now we provide analyses of the EGR3 regulome, which we assessed through binding and expression target analysis of an EGR3-overexpressing t(4;11) cell culture model. Our data identify EGR3 as a regulator of early B-lineage commitment. Principal component analysis of 50 KMT2A-r iALL patients at diagnosis and 18 at relapse provided strictly dichotomous separation of patients based on the expression of four B-lineage genes. Absence of B-lineage gene expression translates to more than two-fold poorer long-term event-free survival. In conclusion, our study presents four B-lineage genes with prognostic significance, suitable for gene expression-based risk stratification of KMT2A-r iALL patients.
Keyphrases
- gene expression
- end stage renal disease
- free survival
- acute lymphoblastic leukemia
- genome wide
- newly diagnosed
- ejection fraction
- chronic kidney disease
- prognostic factors
- poor prognosis
- dna methylation
- single cell
- acute myeloid leukemia
- peritoneal dialysis
- type diabetes
- coronary artery disease
- electronic health record
- hepatitis b virus
- machine learning
- cardiovascular disease
- transcription factor
- data analysis
- acute respiratory distress syndrome
- long non coding rna
- respiratory failure
- bioinformatics analysis