Inactivation of Notch signaling by targeting the γ-secretase complex member Nicastrin in mouse HSCs resulted in an aberrant accumulation of granulocyte/monocyte progenitors in peripheral blood, spleen and liver, diagnostic of the induction of chronic myelomonocytic leukemia (CMML)-like disease. This evidence concerns the gene NCSTN and chronic myelomonocytic leukemia.