Inferring the initiation and development of myeloproliferative neoplasms.

Abstract

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-<i>JAK2^V617F</i> and <i>CALR^m</i>-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 <i>CALR^m</i> mutations tend to occur later in life than <i>JAK2^V617F</i>. Our results confirm the higher proliferative advantage of the <i>CALR^m</i> malignant clone compared to <i>JAK2^V617F</i>. Furthermore, we illustrate how mathematical modeling and Bayesian inference can be used for setting up early screening strategies.