The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia

Blood. 2007 Dec 1;110(12):4073-6. doi: 10.1182/blood-2007-06-095554. Epub 2007 Aug 21.

Abstract

We report the molecular and cytogenetic characterization of a novel variant of acute promyelocytic leukemia (APL). The bone marrow showed 88% hypergranular promyelocytes, and the karyotype was 47,XY,+22 [5]/46,XY[30]. Fluorescence in situ hybridization (FISH) indicated disruption and deletion of the 5'-end of the RARA gene. Treatment with all-trans retinoic acid, idarubicin, and arsenic trioxide induced cytogenetic complete remission without morphologic evidence of residual leukemia. The diagnostic marrow was negative for PML-RARA transcripts by reverse transcription-polymerase chain reaction (RT-PCR), but an atypical product was observed. Sequencing showed partial homology to the PRKAR1A gene, encoding the regulatory subunit type I-alpha of cyclic adenosine monophosphate-dependent protein kinase. RT-PCR using specific primers for PRKAR1A and RARA amplified 2 transcript splice variants of a PRKAR1A-RARA fusion gene, and PRKAR1A and RARA FISH probes confirmed the fusion. This novel PRKAR1A-RARA gene rearrangement is the fifth variant APL in which the RARA partner gene has been identified and the second known rearrangement of PRKAR1A in a malignant disease. This trial was registered at www.actr.org.au with the Australian Clinical Trials Registry as number 12605000070639.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Arsenic Trioxide
  • Arsenicals / administration & dosage
  • Australia
  • Base Sequence / genetics
  • Bone Marrow / pathology
  • Chromosome Aberrations
  • Clinical Trials as Topic
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics*
  • DNA Mutational Analysis
  • Humans
  • Idarubicin / administration & dosage
  • Leukemia, Promyelocytic, Acute / diagnosis
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology
  • Male
  • Mutant Chimeric Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Oxides / administration & dosage
  • RNA, Messenger / genetics
  • Receptors, Retinoic Acid / genetics*
  • Registries
  • Remission Induction
  • Retinoic Acid Receptor alpha
  • Sequence Deletion / genetics
  • Tretinoin / administration & dosage

Substances

  • Arsenicals
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Mutant Chimeric Proteins
  • Neoplasm Proteins
  • Oxides
  • PRKAR1A protein, human
  • RARA protein, human
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Tretinoin
  • Arsenic Trioxide
  • Idarubicin