LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations

Leukemia. 2010 Oct;24(10):1713-8. doi: 10.1038/leu.2010.163. Epub 2010 Aug 19.


LNK mutation analysis was performed in 61 patients with blast-phase myeloproliferative neoplasms (MPN); post-primary myelofibrosis (PMF) in 41, post-polycythemia vera in 11 and post-essential thrombocythemia in 9 patients. Paired chronic-blast phase sample analysis was possible in 26 cases. Nine novel heterozygous LNK mutations were identified in eight (13%) patients: six exon 2 missense mutations involving codons 215, 220, 223, 229 and 234, a synonymous mutation involving codon 208, and two deletion mutations involving exon 2 (685-691_delGGCCCCG) or exon 5 (955_delA); eight affected the pleckstrin homology (PH) domain. Mutations were detected in six (9.8%) blast-phase samples; chronic-phase sample analysis in four of these revealed the same mutation in one. Mutant LNK was detected in chronic-phase only in two patients and in both chronic-blast phases in one. JAK2V617F was documented in three and IDH2R140Q in one LNK-mutated patients. LNK mutations were not detected in 78 additional patients with chronic-phase MPN enriched for TET2, IDH, JAK2V617F, or MPL-mutated cases. We conclude that LNK mutations (i) target an exon 2 'hot spot' in the PH domain spanning residues E208-D234, (ii) might be more prevalent in blast-phase PMF and (iii) are not mutually exclusive of other MPN-associated mutations but rarely occur in their presence in chronic-phase disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Blast Crisis / genetics*
  • Blast Crisis / pathology
  • Chronic Disease
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Dioxygenases
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Isocitrate Dehydrogenase / genetics*
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Polymerase Chain Reaction
  • Prognosis
  • Proteins / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Receptors, Thrombopoietin / genetics*


  • Adaptor Proteins, Signal Transducing
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Thrombopoietin
  • SH2B3 protein, human
  • MPL protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Dioxygenases
  • TET2 protein, human
  • JAK2 protein, human
  • Janus Kinase 2