title: Evaluation of JAK2 in B and T cell neoplasms: identification of JAK2(V617F) mutation of undetermined significance (JMUS) in the bone marrow of three individuals.
abstract: OBJECTIVE
  The JAK2(V617F) mutation, which has been found in patients with myeloproliferative disorders (MPD), has not yet been evaluated in lymphoproliferative disorders by any adequately sensitive techniques.
  
  
  METHODS
  We investigated whether low levels of JAK2(V617F) are present in lymphoid neoplasms using a highly sensitive and highly specific amplification refractory mutation system PCR (ARMS-PCR) assay.
  
  
  RESULTS
  While 234 of 237 cases did not carry the JAK2(V617F) allele, it was identified in the bone marrow of 3 B cell lymphoma patients. The mutation was found to be neither associated with the lymphomas per se, nor with any signs, symptoms or laboratory findings of MPD. Moreover, JAK2(V617F) appeared subsequently in the peripheral blood of 2 of the 3 patients.
  
  
  CONCLUSIONS
  These findings suggest that JAK2(V617F) arises in the bone marrow of individuals before clinical manifestation of any myeloid disorders. Presence of JAK2(V617F) in bone marrow might therefore increase the risk of future MPD development, just as monoclonal gammopathy of undetermined significance (MGUS) increases the risk of multiple myeloma. We term this phenomenon 'JAK2(V617F) of undetermined significance' (JMUS). Its clinical significance remains to be determined. To our knowledge, these findings represent the first identification of JAK2(V617F) in the bone marrow of patients without myeloid malignancies.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. lyw2001@med.cornell.edu
authors.forename: Y Lynn
authors.initials: YL
authors.lastname: Wang
authors.forename: Joong W
authors.initials: JW
authors.lastname: Lee
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Kui
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells / Q000201:enzymology; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000032:analysis / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D016609:Neoplasms, Second Primary; D017354:Point Mutation; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2