The JAK2 exon 12 mutations: A comprehensive review

  title={The JAK2 exon 12 mutations: A comprehensive review},
  author={Linda M Scott},
  journal={American Journal of Hematology},
  • L. Scott
  • Published 1 August 2011
  • Biology
  • American Journal of Hematology
A variety of acquired mutations targeting JAK2 exon 12 are present in those patients with the myeloproliferative neoplasm, polycythemia vera, that lack the more common JAK2V617F mutation. Both mutation types perturb erythropoiesis, with individuals presenting with a raised hematocrit, reduced serum erythropoietin levels, and erythropoietin‐independent erythroid progenitor cells. However, there are also phenotypic differences that, until recently, precluded a significant proportion of patients… 
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The pros and cons of a molecular classification and its potential utility in diagnosis, prognosis, and therapeutics are discussed.
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Current knowledge of molecular abnormalities of MPNs are summarized and their role for diagnosis and prognosis is discussed.
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Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations.
The finding of clonal heterogeneity is compatible with the hypothesis that additional clonal events are involved in the pathogenesis of PV and indicates that JAK2-V617F is a viable treatment option for polycythemia vera.
Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias.
The data suggest that molecular testing of JAK2 mutations should not be restricted to the V617F and exon 12 mutations, but perhaps should extend to most of the pseudokinase domain coding region as well.
The frequency of JAK2 exon 12 mutations in idiopathic erythrocytosis patients with low serum erythropoietin levels
JAK2 exon 12 mutations were detected in 27% of patients with low serum Epo levels, all of whom had Epo-independent erythroid progenitors, and patients presenting with either of these features should be tested for the presence of a JAK2 mutation.
A gain-of-function mutation of JAK2 in myeloproliferative disorders.
Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders.
Mutant Janus kinase 2 (JAK2) has increased kinase activity, renders BaF3 cells cytokine independent, and produces erythrocytosis in patients with myeloproliferative disorders.
Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders.
Several somatic mutations of JAK2 exon 12 can be found in a myeloproliferative disorder that is mainly characterized by erythrocytosis, as detected in patients with polycythemia vera and familial PV.
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
Detection of low allele burden of JAK2 exon 12 mutations using TA-cloning in patients with erythrocytosis.
The biological implications of unknown single nucleotide substitution of the JAK2 exon 12 with low clonal burden in erythrocytosis patients are clarified.