title: Identification of DNA rearrangements at the retinoic acid receptor-alpha (RAR-alpha) locus in all patients with acute promyelocytic leukemia (APL) and mapping of APL breakpoints within the RAR-alpha second intron. Italian Cooperative Study Group "GIMEMA".
abstract: Seventy patients with acute promyelocytic leukemia (APL) were characterized at the DNA level using genomic retinoic acid receptor-alpha (RAR-alpha) probes on Southern blot experiments. Sixty-two cases were defined as M3 according to the French-American-British (FAB) criteria, and eight had a diagnosis of microgranular or variant (M3v) APL. The use of two restriction enzymes and three probes exploring the second intron of the RAR-alpha gene allowed us to detect specific abnormal DNA fragments in every case, with clustering of rearrangements within the 20-kb intronic region between RAR-alpha exons II and III. A more detailed mapping of APL breakpoints was performed in 52 cases in which three EcoRI subregions of the RAR-alpha second intron were analyzed with corresponding probes. Comparison of clinical and hematological features in the three subgroups of patients with distinct RAR-alpha breakpoints did not show significant differences regarding age, peripheral blood (PB) counts, presence of coagulopathy, or FAB classification (M3 v M3v). Interestingly, a significant difference was observed in the M/F ratio of the three subgroups, with a higher incidence of rearrangements at the 5' end of the RAR-alpha second intron in female patients, and more frequent 3' breakpoints in males. The results of this study indicate that a unique genomic alteration consistently occurs on the 17q- derivative of the APL specific t(15;17) aberration. Moreover, the clinical relevance of RAR-alpha gene analysis both at diagnosis and in follow-up studies is further emphasized.
authors.affiliation: Human Biopathology Department, University La Sapienza, Roma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Diverio
authors.forename: F
authors.initials: F
authors.lastname: Lo Coco
authors.forename: F
authors.initials: F
authors.lastname: D'Adamo
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: M
authors.initials: M
authors.lastname: Fagioli
authors.forename: F
authors.initials: F
authors.lastname: Grignani
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
authors.forename: V
authors.initials: V
authors.lastname: Rossi
authors.forename: G
authors.initials: G
authors.lastname: Avvisati
authors.forename: M C
authors.initials: MC
authors.lastname: Petti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics*; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D007438:Introns; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid
chemical_list: D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D004247:DNA; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII