We report a novel gain-of-function JAK2 exon 12 insertion mutation in a patient with idiopathic erythrocytosis and low serum erythropoietin level. To date, only rare cases of such mutations have been reported in the JAK2 exon 12. Using computer-based structural modelling we propose that this mutation causes the loss of the JAK2 auto-inhibition step, leading to the constitutive activation of JAK2 tyrosine kinase-dependent activity. Our model-based hypothesis provides a useful approach for the investigation of the phenotype-genotype relationship in myeloproliferative disorders involving JAK2.

Loss of the JAK2 intramolecular auto-inhibition mechanism is predicted by structural modeling of a novel exon 12 insertion mutation in a case of Idiopathic Erythrocytosis

GIORGETTI, ALEJANDRO;
2008-01-01

Abstract

We report a novel gain-of-function JAK2 exon 12 insertion mutation in a patient with idiopathic erythrocytosis and low serum erythropoietin level. To date, only rare cases of such mutations have been reported in the JAK2 exon 12. Using computer-based structural modelling we propose that this mutation causes the loss of the JAK2 auto-inhibition step, leading to the constitutive activation of JAK2 tyrosine kinase-dependent activity. Our model-based hypothesis provides a useful approach for the investigation of the phenotype-genotype relationship in myeloproliferative disorders involving JAK2.
JAK 2; Idiopathic Erythrocytosis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/315110
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