NEW YORK (Reuters Health) - A single-point mutation in the JAK2 cytoplasmic tyrosine kinase is frequently present in patients with three hematological malignant diseases -- polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis, British investigators report.
All three disorders are thought to be associated with transformation of a multipotent hemopoietic stem cell, Dr. Anthony R. Green, at the University of Cambridge, and associates report in the March 19th issue of The Lancet.
They note that erythroid and myeloid progenitor cells from patients with the three diseases are hypersensitive to several different growth factors. They therefore postulated that a signaling component downstream of multiple growth-factor receptors might be the culprit in the growth abnormalities. According to the authors, the JAK2 tyrosine kinase fits that bill.
Gene sequencing and allele-specific polymerase chain reaction testing of DNA obtained from patients’ blood samples revealed a single point mutation (Val617Phe) in JAK2 in 71 of 73 (97%) patients with polycythemia vera, 29 of 51 (57%) of those with essential thrombocythemia, and 8 of 16 (50%) with idiopathic myelofibrosis.
The same point mutation was absent in specimens from 90 patients with diabetes (controls).
When the investigators grew hematopoietic progenitor cell colonies from four patients, the Val617Phe mutation was identified in both granulocyte-macrophage colonies and erythroid colonies, “showing that it arises in a multipotent progenitor capable of giving rise to both erythroid and myeloid lineages.”
These findings could lead to new diagnostic tests for myeloproliferative disorders, as well as treatments featuring the development of JAK2 inhibitors, the authors suggest.
Source: Lancet 2005;365:1054-1061. [ Google search on this article ]
MeSH Headings:Bone Marrow Cells: Hematopoietic Stem Cells: Membrane Proteins: Receptors, Cell Surface: Polymerase Chain Reaction: Receptors, Growth Factor: Receptors, PeptideCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
