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.

Identification of DNA Rearrangements at the Retinoic Acid Receptor-a (RAR-a) Locus in all Patients With Acute Promyelocytic Leukemia (APL) and mapping of APL Breakpoints within the RAR-a second intron / Daniela, Diverio; LO COCO, Francesco; Francesca, D’Adamo; Andrea, Biondi; Marta, Fagioli; Francesco, Grignani; Alessandro, Rambaldi; Vincenzo, Rossi; Avvisati, Giuseppe; Maria C., Petti; Testi, Anna Maria; Vincenzo, Liso; Giorgina, Specchia; Giuseppe, Fioritoni; Anna, Recchia; Francesco, Frassoni; Stefania, Ciolli; Pier Giuseppe, Pelicci. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 79:(1992), pp. 3331-3336.

Identification of DNA Rearrangements at the Retinoic Acid Receptor-a (RAR-a) Locus in all Patients With Acute Promyelocytic Leukemia (APL) and mapping of APL Breakpoints within the RAR-a second intron

LO COCO, Francesco;AVVISATI, Giuseppe;TESTI, Anna Maria;
1992

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.
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Identification of DNA Rearrangements at the Retinoic Acid Receptor-a (RAR-a) Locus in all Patients With Acute Promyelocytic Leukemia (APL) and mapping of APL Breakpoints within the RAR-a second intron / Daniela, Diverio; LO COCO, Francesco; Francesca, D’Adamo; Andrea, Biondi; Marta, Fagioli; Francesco, Grignani; Alessandro, Rambaldi; Vincenzo, Rossi; Avvisati, Giuseppe; Maria C., Petti; Testi, Anna Maria; Vincenzo, Liso; Giorgina, Specchia; Giuseppe, Fioritoni; Anna, Recchia; Francesco, Frassoni; Stefania, Ciolli; Pier Giuseppe, Pelicci. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 79:(1992), pp. 3331-3336.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/424757
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