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Loss of the JAK2 intramolecular auto‐inhibition mechanism is predicted by structural modelling of a novel exon 12 insertion mutation in a case of idiopathic erythrocytosis
Author(s) -
Albiero Elena,
Madeo Domenico,
Ruggeri Marco,
Bernardi Martina,
Giorgetti Alejandro,
Rodeghiero Francesco
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07180.x
Subject(s) - exon , mutation , erythropoietin , phenotype , myeloproliferative disorders , cancer research , janus kinase 2 , tyrosine kinase , erythropoietin receptor , genetics , medicine , biology , phosphorylation , receptor , gene
Summary 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 .