Gene regulation in t(6;9) AML resembles that of FLT3-ITD/NPM1 AML with an altered HOX/MEIS axis [RNA-seq]
Acute Myeloid Leukemia (AML) represents a heterogeneous group of hematological malignancies. The t(6;9)(p23;q34) translocation, giving rise to the DEK::NUP214 fusion protein, is a rare mutation which produces a highly aggressive AML associated with extremely poor prognosis. Here, we utilise genome-wide chromatin accessibility to elucidate how a normal gene regulatory networks is disrupted by DEK::NUP214. We find that DEK::NUP214 AML forms a specific GRN related to that of mutant NPM1 AML, but also displays an elevated leukemic stem cell signature, suggesting both similar and unique therapeutic vulnerabilities. Overall design: Here, we utilise genome-wide chromatin accessibility  by DNase-1-seq to elucidate how a normal gene regulatory networks is disrupted by DEK::NUP214. We find that DEK::NUP214 AML forms a specific GRN related to that of mutant NPM1 AML, but also displays an elevated leukemic stem cell signature, suggesting both similar and unique therapeutic vulnerabilities.