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Two clinical phenotypes in polycythemia vera.

Jerry L Spivak1, Michael Considine, Donna M Williams

  • 1From the Division of Hematology, Department of Medicine (J.L.S., D.M.W., O.R., A.R.M.), Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center (M.C.), and the Basic Science Institute (C.C.T.), Johns Hopkins University School of Medicine, Baltimore; the Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago (C.J.); and the Department of Mathematics and Statistics, College of New Jersey, Ewing (M.F.O.).

The New England Journal of Medicine
|August 28, 2014
PubMed
Summary
This summary is machine-generated.

Polycythemia vera gene expression differs between sexes. A new molecular classification method accurately predicts disease behavior independently of JAK2 V617F mutation status.

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Area of Science:

  • Hematology
  • Molecular Biology
  • Genomics

Background:

  • Polycythemia vera is linked to the JAK2 V617F mutation.
  • The impact of this mutation on CD34+ hematopoietic stem cells is not fully understood.

Purpose of the Study:

  • To investigate gene expression differences in polycythemia vera patients.
  • To develop a molecular classification method for predicting disease behavior.

Main Methods:

  • Gene expression analysis using oligonucleotide microarrays in CD34+ cells from 19 polycythemia vera patients.
  • Correction for sex as a confounding factor.
  • Unsupervised hierarchical clustering and supervised classification for patient grouping.

Main Results:

  • Identified 102 differentially regulated genes common to both sexes.
  • Patients were classified into two distinct groups based on gene expression, correlating with disease duration, clinical features, and outcomes.
  • Classification accuracy was 100% using a top-scoring-pair classifier.

Conclusions:

  • Developed a sex-independent molecular classification for polycythemia vera.
  • Identified novel molecular pathways beyond the JAK2 pathway for potential targeted therapies.