Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation

S. Licciulli, V. Cambiaghi, G. Scafetta, A. M. Gruszka, M. Alcalay

Research output: Contribution to journalArticle

Abstract

Terminal differentiation of blood cells requires the concerted action of a series of transcription factors that are expressed at specific stages of maturation and function in a cell-type and dosage-dependent manner. Leukemogenic oncoproteins block differentiation by subverting the normal transcriptional status of hematopoietic precursor cells. Pirin (PIR) is a putative transcriptional regulator whose expression is silenced in cells bearing the acute myeloid leukemia-1 eight-twenty-one (AML1/ETO) and promyelocytic leukemia/retinoic acid receptor (PML/RAR) leukemogenic fusion proteins. A role for PIR in myeloid differentiation has not to date been reported. In this study we show that PIR expression is significantly repressed in a large proportion of acute myeloid leukemias (AMLs), regardless of subtype or underlying karyotypic abnormalities. We show that PIR expression increases during in vitro myeloid differentiation of primary hematopoietic precursor cells, and that ablation of PIR in the U937 myelomonocytic cell line or in murine primary hematopoietic precursor cells results in impairment of terminal myeloid differentiation. Gene expression profiling of U937 cells after knockdown of PIR revealed increased expression of genes associated with the early phases of hematopoiesis, in particular, homeobox A (HOXA) genes. Our results suggest that PIR is required for terminal myeloid maturation, and its downregulation may contribute to the differentiation arrest associated with AML.

Original languageEnglish
Pages (from-to)429-437
Number of pages9
JournalLeukemia
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • Acute myeloid leukemia
  • Myeloid differentiation
  • Pirin
  • Transcription

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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