The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia.
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.
Catalano
Alberto
A
Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia. alberto.catalano@email.cs.nsw.gov.au
Dawson
Mark A
MA
Somana
Karthiga
K
Opat
Stephen
S
Schwarer
Anthony
A
Campbell
Lynda J
LJ
Iland
Harry
H
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001315:Australia; D001483:Base Sequence / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D002986:Clinical Trials as Topic; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D050506:Mutant Chimeric Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010087:Oxides / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012042:Registries; D012074:Remission Induction; D000072482:Retinoic Acid Receptor alpha; D017384:Sequence Deletion / Q000235:genetics; D014212:Tretinoin / Q000008:administration & dosage
D001152:Arsenicals; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D050506:Mutant Chimeric Proteins; D009363:Neoplasm Proteins; D010087:Oxides; C517834:PRKAR1A protein, human; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000077237:Arsenic Trioxide; D015255:Idarubicin