The relationship between S100A8 signaling axis and thrombopoiesis could be best explored in CALR-mutated murine models, which would also help clarify several key questions originated from this work, including whether increased S100A8 does accelerate MF transformation, whether S100A8 plays an essential role in CALRDEL mutation-associated MPN pathogenesis while it becomes dispensable in CALRINS mutation-induced disease propagation, and whether S100A8 could create a more inflammatory milieu in the CALRDEL-mutated BM. The gene discussed is CALR; the disease is myeloproliferative disorder.