Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 37, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2120374119
Keywords
mathematical modeling of cell populations; myeloproliferative neoplasms; JAK2/CALR mutations; cancer early detection; approximate bayesian computation
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Funding
- Prism Project - Agence Nationale de la Recherche [ANR-18-IBHU-0002]
- Institut Thematique Multi-Organismes (ITMO) Cancer of Aviesan
- INSERM
- INCA Plbio
- Ligue Nationale Contre le Cancer
- MENRT grant then from Ligue Nationale Contre le Cancer
- Agence Nationale de la Recherche (ANR) [ANR-18-IBHU-0002] Funding Source: Agence Nationale de la Recherche (ANR)
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This study investigates the initiation and dynamics of blood cancer through mathematical modeling and statistical inference. The findings suggest that CALR(m) mutations tend to occur later in life compared to JAK2(V617F), confirming the higher proliferative advantage of the CALR(m) malignant clone.
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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