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Identification and Analysis of Mouse Erythroid Progenitors using the CD71/TER119 Flow-cytometric Assay
15:32

Identification and Analysis of Mouse Erythroid Progenitors using the CD71/TER119 Flow-cytometric Assay

Published on: August 5, 2011

Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary

Konrad Aumann1, Anna-Verena Frey, Annette M May

  • 1Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany.

Blood
|May 15, 2013
PubMed

Insights

Nuclear factor erythroid 2 (NF-E2) mislocalization in myeloproliferative neoplasms (MPNs) distinguishes essential thrombocythemia (ET) from primary myelofibrosis (PMF). This finding supports NF-E2 immunohistochemistry as a reliable diagnostic tool for MPN classification.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Pathology

Background:

  • The World Health Organization (WHO) classification categorizes myeloproliferative neoplasms (MPNs) into essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPN, unclassifiable (MPN,U).
  • Distinguishing between ET and early, prefibrotic PMF is clinically significant due to differing prognoses, yet can be diagnostically challenging.
  • Aberrant expression of the transcription factor nuclear factor erythroid 2 (NF-E2) has been previously observed in MPN patients.

Purpose of the Study:

  • To investigate the diagnostic utility of nuclear factor erythroid 2 (NF-E2) localization in differentiating ET from PMF.
  • To establish a quantitative threshold for NF-E2 nuclear localization to support differential diagnosis in MPNs.

Main Methods:

  • Immunohistochemistry was employed to assess NF-E2 localization in bone marrow biopsies from MPN patients.
  • Quantitative analysis of nuclear NF-E2 staining was performed.
  • Statistical analysis, including bootstrapping and interobserver concordance assessment, was utilized to validate findings.

Main Results:

  • Aberrant NF-E2 mislocalization was observed in PMF cells compared to ET cells.
  • A threshold of 20% nuclear NF-E2 staining demonstrated high statistical significance in discriminating between ET and PMF.
  • This NF-E2 staining cutoff achieved 92% accuracy in classifying MPN,U cases upon follow-up and showed high interobserver concordance (Spearman's rho = 0.727).

Conclusions:

  • Quantitative NF-E2 immunohistochemistry is a reliable tool for supporting the differential diagnosis between ET and PMF.
  • NF-E2 mislocalization serves as a significant biomarker for distinguishing these MPN subtypes.
  • This method offers a valuable adjunct to existing diagnostic criteria for MPNs.

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