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.

Diverio, D., LO COCO, F., D'Adamo, F., Biondi, A., Fagioli, M., Grignani, F., et al. (1992). 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". BLOOD, 79(12), 3331-6.

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"

LO COCO, FRANCESCO;
1992-06-15

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.
15-giu-1992
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - MALATTIE DEL SANGUE
English
Adolescent; Adult; Aged; Blotting, Southern; Carrier Proteins; Child; Child, Preschool; Chromosome Mapping; DNA; Deoxyribonuclease EcoRI; Deoxyribonuclease HindIII; Exons; Female; Humans; Infant; Introns; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Receptors, Retinoic Acid; Gene Rearrangement
Diverio, D., LO COCO, F., D'Adamo, F., Biondi, A., Fagioli, M., Grignani, F., et al. (1992). 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". BLOOD, 79(12), 3331-6.
Diverio, D; LO COCO, F; D'Adamo, F; Biondi, A; Fagioli, M; Grignani, F; Rambaldi, A; Rossi, V; Avvisati, G; Petti, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/161057
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