Molecular docking of CALR GBD was conducted to search for mutant CALR inhibitors. (A) Structural model of human CALR. Colored surface representations indicate experimentally identified interaction sites: N-glycan binding site (cyan), ATP binding site (magenta), and Ca2⁺ binding site (gray). (B) Cytokine dose response of the GBD-mutated Ba/F3-MPL cells. Ba/F3-MPL cells were transduced with pMSCV-puro constructs carrying CALR WT, CALR del52, and lysine 111– and aspartic acid 317– mutated CALR del52. The transduced cells were cultured with different concentrations of the cytokines, and the cell viability was detected after 72 hours. WEHI-3B–conditioned media and TPO-conditioned media were used as murine IL-3 and human TPO supplements (n = 6). Data are shown as mean ± standard deviation. (C) In silico modeling of the CALR GBD domain. The globular domain of CALR is shown (α-helix, red; β-sheets, yellow). A grid box is defined at the GBD domain for the docking prediction (pink area). The cocrystalized tetrasaccharide molecule (carbon molecule, dark green; oxygen molecule, red; hydrogen molecule, gray) is displayed and interacts with the CALR GBD. RLU, relative luminescence unit.