PMID- 17712046
OWN - NLM
STAT- MEDLINE
DCOM- 20071226
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 12
DP  - 2007 Dec 1
TI  - The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia.
PG  - 4073-6
AB  - 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.
FAU - Catalano, Alberto
AU  - Catalano A
AD  - Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia. 
      alberto.catalano@email.cs.nsw.gov.au
FAU - Dawson, Mark A
AU  - Dawson MA
FAU - Somana, Karthiga
AU  - Somana K
FAU - Opat, Stephen
AU  - Opat S
FAU - Schwarer, Anthony
AU  - Schwarer A
FAU - Campbell, Lynda J
AU  - Campbell LJ
FAU - Iland, Harry
AU  - Iland H
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20070821
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Arsenicals)
RN  - 0 (Cyclic AMP-Dependent Protein Kinase RIalpha Subunit)
RN  - 0 (Mutant Chimeric Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oxides)
RN  - 0 (PRKAR1A protein, human)
RN  - 0 (RARA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 5688UTC01R (Tretinoin)
RN  - S7V92P67HO (Arsenic Trioxide)
RN  - ZRP63D75JW (Idarubicin)
SB  - IM
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
MH  - Arsenic Trioxide
MH  - Arsenicals/administration & dosage
MH  - Australia
MH  - Base Sequence/genetics
MH  - Bone Marrow/pathology
MH  - Chromosome Aberrations
MH  - Clinical Trials as Topic
MH  - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/*genetics
MH  - DNA Mutational Analysis
MH  - Humans
MH  - Idarubicin/administration & dosage
MH  - Leukemia, Promyelocytic, Acute/diagnosis/drug therapy/*genetics/pathology
MH  - Male
MH  - Mutant Chimeric Proteins/*genetics
MH  - Neoplasm Proteins/*genetics
MH  - Oxides/administration & dosage
MH  - RNA, Messenger/genetics
MH  - Receptors, Retinoic Acid/*genetics
MH  - Registries
MH  - Remission Induction
MH  - Retinoic Acid Receptor alpha
MH  - Sequence Deletion/genetics
MH  - Tretinoin/administration & dosage
EDAT- 2007/08/23 09:00
MHDA- 2007/12/27 09:00
CRDT- 2007/08/23 09:00
PHST- 2007/08/23 09:00 [pubmed]
PHST- 2007/12/27 09:00 [medline]
PHST- 2007/08/23 09:00 [entrez]
AID - S0006-4971(20)42227-X [pii]
AID - 10.1182/blood-2007-06-095554 [doi]
PST - ppublish
SO  - Blood. 2007 Dec 1;110(12):4073-6. doi: 10.1182/blood-2007-06-095554. Epub 2007 
      Aug 21.