title: Clonal analyses define the relationships between chromosomal abnormalities and JAK2V617F in patients with Ph-negative myeloproliferative neoplasms.
abstract: OBJECTIVE
  JAK2V617F occurs in approximately 93% of patients with polycythemia vera and approximately 50% of patients with either primary myelofibrosis or essential thrombocythemia. Chromosomal abnormalities are detected in 50% of patients with primary myelofibrosis, 29% with polycythemia vera, and 8% to 10% with essential thrombocythemia. The relationship between the presence of such chromosomal abnormalities and the JAK2V617 allele burden, and the role that each of these genetic events play in the origins and progression of the myeloproliferative neoplasms (MPNs), remain unclear.
  
  
  METHODS
  Individual hematopoietic colonies were assayed in vitro from the CD34(+) cells of six JAK2V617F-positive MPN patients with marker chromosomal abnormalities. Colonies were simultaneously analyzed for JAK2 genotype and chromosomal abnormalities.
  
  
  RESULTS
  Among the 248 colonies assayed from cultures containing 500 CD34(+) cells, chromosomal abnormalities were detected in 5% of colonies with wild-type JAK2, 32% of JAK2V617F heterozygous colonies and 56% of JAK2V617F homozygous colonies. Overall, 92% of chromosomally abnormal colonies were also JAK2V617F homozygous. Although 54 colonies contained wild-type JAK2 exclusively, 4 of these colonies were characterized by chromosomal abnormalities.
  
  
  CONCLUSIONS
  This study indicates that MPN hematopoietic progenitor cells do not necessarily always acquire genetic events in the same sequence. (Chromosomally abnormal progenitor cells are closely associated with JAK2V617F homozygosity; p=0.0001.). Chromosomal abnormalities such as +8, +9 can occasionally precede acquisition of JAK2V617F. These findings support the existence of earlier genetic events that precede JAK2V617F or cytogenetic abnormalities in MPN hematopoietic progenitor cells.
authors.affiliation: Division of Hematology and Oncology, The Myeloproliferative Disorders Program, Tisch Cancer Institute, New York, NY, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Amanda
authors.initials: A
authors.lastname: LeBlanc
authors.forename: Steven
authors.initials: S
authors.lastname: Gruenstein
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Xu
authors.forename: John
authors.initials: J
authors.lastname: Mascarenhas
authors.forename: Brenda
authors.initials: B
authors.lastname: Panzera
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Wisch
authors.forename: Charles
authors.initials: C
authors.lastname: Parker
authors.forename: Judith D
authors.initials: JD
authors.lastname: Goldberg
authors.forename: Josef
authors.initials: J
authors.lastname: Prchal
authors.forename: Ronald
authors.initials: R
authors.lastname: Hoffman
authors.forename: Vesna
authors.initials: V
authors.lastname: Najfeld
mesh_terms: D000368:Aged; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011087:Polycythemia Vera / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2