Fig. 1

a Pedigree of two independent families harboring JAK2 p.G571S. The ALL patients are marked with a red triangle, while the transmission of the identified target mutations is highlighted with red symbols (JAK2 = circle; STAT3 = +; trisomy 21 = #). b Domain organization of JAK2 and STAT3 proteins. Identified mutations (red) and the known activating JAK2 mutation p.V617F (black), which was used as a control, are highlighted. c Overview of the STAT3-WT (gray) with bound DNA (orange). The blue rectangle indicates the region with the residues of interest (sticks). A close-up depicts the mutated region in STAT3-WT (gray) and the p.K370R variant (dark green). While in the STAT3-WT, p.K370 only interacts with p.E455, p.R370 of the p.K370R variant interacts with both p.E442 and p.E455 as indicated by the yellow lines. The mutation of lysine to arginine also distorts the local backbone conformation. d Homology model of the p.G571S variant in the JAK2 protein (green). P.S571 (sticks) is located in a loop between two β-strands next to p.Y570 (sticks), which is one of the most important phosphorylation sites in JAK2