Figure 1.

Impact of germline pathogenic variants in GATA2 on hematopoietic network and leukemic transformation. Schematic of the role of GATA2 interactions in transcriptional networks in normal hematopoiesis including interacting partners, target genes and upstream regulators. GATA2, a common target of aberration in leukemias, leads to inappropriate transcriptional programs resulting in TF dysregulation, impaired differentiation, and subsequent expansion of immature cell populations to initiate malignancy. While based on published data, the figure is somewhat hypothetical as each hematopoietic TF gene regulatory region is bound by a different combination, clustering, and arrangement of these TFs. Pathogenic germline variants (lightning bolt) may lead to disrupted DNA binding and/or interactions with other TFs (dashed arrows) resulting in a range of impacts on downstream target genes that may include disruptions to additive, synergistic and/or inhibitory transcriptional events. This image was created using BioRender.com.