The European Hematology Association (EHA) Congress is a high-level forum for original data, hematological innovation, and evidence-based research of primary clinical relevance. This year, the program featured our very own Sofia Gialesaki, who spoke to thousands of clinicians and scientists about her research during the prestigious Presidential Symposium! Her top-ranking abstract, titled “Deciphering the role of RUNX1 isoforms in the development of transient abnormal myelopoiesis“, earned her a YoungEHA Best Abstract Award. To view Sofia’s talk online, visit the EHA Library website.
Transient abnormal myelopoiesis (TAM) and Down syndrome myeloid leukemia (ML-DS) are driven by the interaction between trisomy 21 and GATA1s in fetal hematopoietic cells. Aiming to delineate the mechanisms underlying this cooperation, our group conducted a CRISPR-Cas9 gene essentiality screen of the 218 coding genes on human chromosome 21, revealing a strong and specific RUNX1 dependency in an ML-DS cell line (CMK) compared to non-DS leukemia cells (K562). Further analysis revealed that the equilibrium of RUNX1 isoforms is deregulated in ML-DS patient blasts compared to normal hematopoietic stem and progenitor cells. Through a series of in vitro and in vivo experiments in normal and leukemic cells, we showed that RUNX1 isoform dysregulation synergizes with GATA1s to drive leukemogenesis in TAM / ML-DS.