With the use of in vitro cell lines and retroviral mouse models, CALR mutants were found to activate the JAK-STAT signaling in an MPL-dependent manner.11, 12, 13, 14, 15 Although the expression of CALR mutants resulted in pathogenic thrombocytosis in adult mice, whether CALR mutants may disrupt normal hematopoiesis during early development remains unknown. The gene discussed is CALR; the disease is thrombocytosis disease.