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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"
D Diverio, F Lo Coco, F D'Adamo, A Biondi, M Fagioli, F Grignani, A Rambaldi, V Rossi, G Avvisati and MC Petti
Human Biopathology Department, University La Sapienza, Roma, Italy.
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.
Volume 79,
Issue 12,
pp. 3331-3336,
06/15/1992
Copyright © 1992 by The American Society of Hematology
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