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Inferring the initiation and development of myeloproliferative neoplasms.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Sep 13; Vol. 119 (37), pp. e2120374119. Date of Electronic Publication: 2022 Sep 09. - Publication Year :
- 2022
-
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 <superscript>V617F</superscript> and CALR <superscript>m</superscript> -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 <superscript>m</superscript> mutations tend to occur later in life than JAK2 <superscript>V617F</superscript> . Our results confirm the higher proliferative advantage of the CALR <superscript>m</superscript> malignant clone compared to JAK2 <superscript>V617F</superscript> . Furthermore, we illustrate how mathematical modeling and Bayesian inference can be used for setting up early screening strategies.
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 119
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 36083966
- Full Text :
- https://doi.org/10.1073/pnas.2120374119