A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene

Int J Hematol. 2015 Dec;102(6):713-8. doi: 10.1007/s12185-015-1857-2. Epub 2015 Sep 5.

Abstract

We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed with MS, as the tumor cells were positive for myeloperoxidase and CD68 but negative for CD163. After treatment with steroids and radiation, the size of the tumor was markedly reduced and peripheral blood count was normal. Bone marrow examination showed 89.2% consisted of unclassified promyelocytes characterized by round nuclei and abundant small azurophilic granules but no Auer rods. The results of chromosome analysis showed 46,XY,t(5;17)(q35;q12). Reverse-transcription polymerase chain reaction amplified the NPM1/RARA fusion transcripts derived from a combination of NPM1 exon 4 and RARA exon 5, or of NPM1 exon 1 and RARA exon 5; the latter of these has not been reported previously. Electron microscopic examination of the promyelocyte nuclei showed they were oval with mild nuclear chromatin condensation and small- to medium-sized nucleoli. Hematological and molecular complete remission was attained after induction therapy including all-trans retinoic acid. As MS was also diagnosed in two of the seven other reported cases of APL with NPM1/RARA, MS may occur more frequently in APL with NPM1/RARA than APL with PML/RARA.

Keywords: Acute promyelocytic leukemia; All-trans retinoic acid; Myeloid sarcoma; NPM1/RARA; t(5;17)(q35;q12–21).

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cell Nucleolus / pathology
  • Cell Nucleolus / ultrastructure
  • Cell Nucleus / ultrastructure
  • Chromatin / pathology
  • Chromatin / ultrastructure
  • Exons / genetics
  • Gene Fusion*
  • Granulocyte Precursor Cells / cytology
  • Humans
  • Induction Chemotherapy
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Receptors, Retinoic Acid / genetics*
  • Retinoic Acid Receptor alpha
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Myeloid / diagnosis
  • Sarcoma, Myeloid / therapy
  • Tretinoin / therapeutic use

Substances

  • Chromatin
  • NPM1 protein, human
  • Nuclear Proteins
  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Nucleophosmin
  • Tretinoin