title: Acute promyelocytic leukaemia in patients originating in Latin America is associated with an increased frequency of the bcr1 subtype of the PML/RARalpha fusion gene.
abstract: The PML/RARalpha fusion gene in acute promyelocytic leukaemia (APL) has three subtypes based on the breakpoint site of the PML gene: long (bcr1), short (bcr3) and variable (bcr2) subtypes. The PML/RARalpha fusion protein is involved in the pathogenesis of APL and the breakpoint site of the PML gene might be associated with aetiological factor(s). Because APL is over-represented in patients that originate in Latin America (Latinos), we evaluated whether the distribution of the PML/RARalpha fusion mRNA in this population is different to that reported in non-Latinos. Among 52 APL patients (28 from Mexico and Central America diagnosed in Los Angeles and 24 from Peru, South America), bcr1, bcr2 and bcr3 expression was 75%, 10% and 15% respectively. However, bcr1 breakpoints were significantly higher compared with non-Latino patients (340/654, 52%) reported in four studies. Often bcr1 and bcr2 are reported together; 862 (60%) of 1429 non-Latino APL patients reported in nine studies were either bcr1 or bcr2, compared with 44 (85%) in our 52 Latino patients. This difference was also statistically significant when our patients were compared to each of the individual studies from USA and Europe, but not for a small series from China and Japan. These results suggest that the overrepresentation of APL among Latin American patients can be accounted for by an increase of a single subtype--bcr1, and the breakage sites in the PML gene may not be random but possibly influenced by genetic and/or environmental factor(s).
authors.affiliation: Division of Haematology, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Centre, 14421 Eastlake Avenue, Room 4360, Los Angeles, CA 90033, USA. douer_d@ccnt.hsc.usd.edu
authors.forename: Dan
authors.initials: D
authors.lastname: Douer
authors.forename: Sergio
authors.initials: S
authors.lastname: Santillana
authors.forename: Laleh
authors.initials: L
authors.lastname: Ramezani
authors.forename: Cesar
authors.initials: C
authors.lastname: Samanez
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Slovak
authors.forename: Ming S
authors.initials: MS
authors.lastname: Lee
authors.forename: Kristy
authors.initials: K
authors.lastname: Watkins
authors.forename: Tony
authors.initials: T
authors.lastname: Williams
authors.forename: Carlos
authors.initials: C
authors.lastname: Vallejos
mesh_terms: D000293:Adolescent; D000328:Adult; D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007843:Latin America / Q000208:ethnology; D015473:Leukemia, Promyelocytic, Acute / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr