Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia.

Abstract	The World Health Organization (WHO) classification of myeloproliferative neoplasms (MPNs) comprises several entities including essential thrombocythemia (ET); primary myelofibrosis (PMF); and MPN, unclassifiable (MPN,U). Differential diagnosis between ET and early, prefibrotic PMF can be challenging but is critical because clinical course and outcome vary considerably between these entities. We have previously shown that the transcription factor nuclear factor erythroid 2 (NF-E2) is aberrantly expressed in MPN patients. Here we demonstrate that NF-E2 is mislocalized in PMF cells and that aberrant NF-E2 localization discriminates statistically highly significantly between ET and PMF. A threshold of 20% nuclear NF-E2 staining was cross-validated by ".682+ bootstrapping." Moreover, this cutoff correctly classifies diagnostic bone marrow biopsies of MPN,U patients specified upon follow-up as ET or PMF with 92% accuracy. Because interobserver concordance between independent pathologists was high (Spearman's rank correlation coefficient, 0.727), we propose that quantitative NF-E2 immunohistochemistry represents a diagnostic tool that can reliably support a differential diagnosis between ET and PMF.
Authors	Konrad Aumann, Anna-Verena Frey, Annette M May, Dieter Hauschke, Clemens Kreutz, Jan P Marx, Jens Timmer, Martin Werner, Heike L Pahl
Journal	Blood (Blood) Vol. 122 Issue 1 Pg. 93-9 (Jul 04 2013) ISSN: 1528-0020 [Electronic] United States
PMID	23670178 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, CD CD71 antigen NF-E2 Transcription Factor, p45 Subunit NFE2 protein, human Receptors, Transferrin
Topics	Antigens, CD (metabolism) Biopsy Cohort Studies Diagnosis, Differential Erythroid Cells (metabolism, pathology) Humans Immunohistochemistry (statistics & numerical data) NF-E2 Transcription Factor, p45 Subunit (metabolism) Observer Variation Primary Myelofibrosis (diagnosis, pathology) Prognosis Receptors, Transferrin (metabolism) Thrombocythemia, Essential (diagnosis, pathology) Tissue Banks

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