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The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation
Open accessAbstract
Although a large proportion of patients with polycythemia vera (PV) harbor a valine-to-phenylalanine mutation at amino acid 617 (V617F) in the JAK2 signaling molecule, the stage of hematopoiesis at which the mutation arises is unknown. Here we isolated and characterized hematopoietic stem cells (HSC) and myeloid progenitors from 16 PV patient samples and 14 normal individuals, testing whether the JAK2 mutation could be found at the level of stem or progenitor cells and whether the JAK2 V617F-positive cells had altered differentiation potential. In all PV samples analyzed, there were increased numbers of cells with a HSC phenotype (CD34 + CD38 − CD90 + Lin − ) compared with normal samples. Hematopoietic progenitor assays demonstrated that the differentiation potential of PV was already skewed toward the erythroid lineage at the HSC level. The JAK2 V617F mutation was detectable within HSC and their progeny in PV. Moreover, the aberrant erythroid potential of PV HSC was potently inhibited with a JAK2 inhibitor, AG490.
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Cites
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Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617
Self-citationGranulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
Jamieson, C. H. M., Ailles, L. E., Dylla, S. J., Muijtjens, M., Jones, C., Zehnder, J. L., Gotlib, J., Li, K., Manz, M. G., Keating, A., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040258 · Cited by 1,485
Cited by
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
Mutation in TET2 in Myeloid Cancers
Delhommeau, F., Dupont, S., Valle, V. D., James, C., Trannoy, S., Massé, A., Kosmider, O., Le Couedic, J.-P., Robert, F., Alberdi, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810069 · Cited by 1,776
The Myeloproliferative Disorders
Campbell, P. J., & Green, A. R. (2006) · New England Journal of Medicine · doi:10.1056/nejmra063728 · Cited by 915
Quintás-Cardama, A., Vaddi, K., Liu, P., Manshouri, T., Li, J., Scherle, P. A., Caulder, E., Wen, X., Li, Y., Waeltz, P., et al. (2010) · Blood · doi:10.1182/blood-2009-04-214957 · Cited by 843
Rampal, R., Al-Shahrour, F., Abdel-Wahab, O., Patel, J. P., Brunel, J.-P., Mermel, C. H., Bass, A. J., Pretz, J., Ahn, J., Hricik, T., et al. (2014) · Blood · doi:10.1182/blood-2014-02-554634 · Cited by 428
Metadata
- Authors
- Jamieson, C. H. M., Gotlib, J., Durocher, J. A., Chao, M. P., Mariappan, M. R., Lay, M., Jones, C., Zehnder, J. L., Lilleberg, S. L., & Weissman, I. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-04-18
- Volume
- 103
- Issue
- 16
- Pages
- 6224-6229
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2029818817
- Cited by
- 286
- References
- 2
- FWCI
- 11.95
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. https://app.cochat.ai/papers/10.1073/pnas.0601462103
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- Jamieson, C. H. M., Gotlib, J., Durocher, J. A., Chao, M. P., Mariappan, M. R., Lay, M., Jones, C., Zehnder, J. L., Lilleberg, S. L., & Weissman, I. L. (2006). The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0601462103
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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