The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation
| Autor: | Stan L. Lilleberg, M. Rajan Mariappan, Mark P. Chao, James L. Zehnder, Jeffrey Durocher, Carol Adaire Jones, Marla Lay, Catriona Jamieson, Jason Gotlib, Irving L. Weissman |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Myeloid
Phenylalanine CD34 Antigens CD34 Biology Polycythemia vera hemic and lymphatic diseases Proto-Oncogene Proteins medicine Humans Point Mutation Progenitor cell Polycythemia Vera Protein Kinase Inhibitors Erythroid Precursor Cells Multidisciplinary Janus kinase 2 Valine Janus Kinase 2 Protein-Tyrosine Kinases Tyrphostins Biological Sciences medicine.disease Hematopoietic Stem Cells ADP-ribosyl Cyclase 1 Hematopoiesis Haematopoiesis medicine.anatomical_structure Amino Acid Substitution biology.protein Cancer research Thy-1 Antigens Stem cell |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 103(16) |
| ISSN: | 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|