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Inferring the initiation and development of myeloproliferative neoplasms.

Proceedings of the National Academy of Sciences of the United States of America(2022)

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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- and -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 mutations tend to occur later in life than . Our results confirm the higher proliferative advantage of the malignant clone compared to . Furthermore, we illustrate how mathematical modeling and Bayesian inference can be used for setting up early screening strategies.
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Key words
JAK2/CALR mutations,approximate bayesian computation,cancer early detection,mathematical modeling of cell populations,myeloproliferative neoplasms
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