Myeloproliferative Disorders Associated with Tyrosine Kinase Mutation

Posted by rob on March 25, 2005 under Uncategorized | Be the First to Comment

Myeloproliferative Disorders Associated with Tyrosine Kinase Mutation

Researchers from the UK have identified an acquired single point mutation as the probable cause of more than half the cases of myeloproliferative disorders. The details of this study appeared in the March 19, 2005 issue of the Lancet.

Myeloproliferative disorders currently include polycythemia vera, essential thrombocytosis and idiopathic myelofibrosis. The cause or causes of this group of diseases is unknown. In the past, patients with chronic myeloid leukemia (CML) were included in this group of diseases, but cytogenetic and molecular studies revealed unique cause of CML. Now a similar phenomenon may be occurring with other myeloproliferative disorders.

JAK2 is a tyrosine kinase that has a major role in cell proliferation. The hypothesis of this study was that mutated JAK2 could be responsible for myeloproliferative disorders. Researchers in the study performed molecular genetic studies in 73 patients with polycythemia vera, 51 with essential thrombocytosis, and 16 with idiopathic myelofibrosis. They found that 97% of patients with polycythemia vera had a sincle acquired mutation of JAK2 cytoplasmic tyrosine kinase. The same mutation was present in 57% of patients with essential thrombocytosis and 50% of patients with idiopathic myelofibrosis. They also found this mutation is all erythropoietin-dependent erythroid colonies and present in multipotent cells giving rise to both erythroid and myeloid cells. These authors suggest that identification of mutated JAK2 will assist in classification of myeloproliferative disorders and may provide insight into pathogenesis.

Comments: This study is important, as it could lead to specific therapies for myeloproliferative disorders similar to that observed with the development of Gleevec® for the treatment of CML.

Reference: Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. The Lancet. 2005;365:1054-1061.

Myeloproliferative Disorders Associated with Tyrosine Kinase Mutation