The developmental history of blood cancer begins with mutation acquisition and the resulting malignant clone expansion. The two most prevalent driver mutations found in myeloproliferative neoplasms— JAK2 V617F and CALR m —occur in hematopoietic stem cells, which are highly complex to observe in vivo. To circumvent this difficulty, we propose a method relying on mathematical modeling and statistical inference to determine disease initiation and dynamics. Our findings suggest that CALR m mutations tend to occur later in life than JAK2 V617F . Our results confirm the higher proliferative advantage of the CALR m malignant clone compared to JAK2 V617F . Furthermore, we illustrate how mathematical modeling and Bayesian inference can be used for setting up early screening strategies.