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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— 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.
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Submitted on : Wednesday, November 9, 2022 - 9:48:20 AM
Last modification on : Tuesday, November 22, 2022 - 3:33:12 AM



Gurvan Hermange, Alicia Rakotonirainy, Mahmoud Bentriou, Amandine Tisserand, Mira El-Khoury, et al.. Inferring the initiation and development of myeloproliferative neoplasms. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (37), ⟨10.1073/pnas.2120374119⟩. ⟨hal-03844872⟩



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