Molecular heterogeneity of the PML gene rearrangement in acute promyelocytic leukemia: prevalence and clinical significance.
We determined the breakpoints of the RAR-alpha and PML genes in acute promyelocytic leukemia (APL) cells from 40 patients using Southern blot analysis. We also analyzed the relationship between the location of breakpoints, the clinical features of APL and the response to all-trans retinoic acid (ATRA). While the breakpoints of the RAR-alpha gene were consistently within intron 2, we found two major clusters in the breakpoints of the PML gene. The two breakpoint clusters in the PML gene were separated by 10 kb; 5' breakpoints were in intron 3, and 3' breakpoints were around introns 5 and 6. Twenty percent of the patients had 5' breakpoints in the PML gene and 70% had 3' breakpoints. No rearrangement was observed in the remaining 10% of patients in spite of the presence of t(15;17) translocation. There was no relationship between the location of the PML breakpoints, the clinical features at diagnosis and the response to ATRA.
Department of Internal Medicine, Nagoya University Branch Hospital.
H
H
Fukutani
T
T
Naoe
H
H
Yoshida
S
S
Yamamori
R
R
Ohno
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D015342:DNA Probes / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D015995:Prevalence; D018168:Receptors, Retinoic Acid; D015183:Restriction Mapping; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology
D002352:Carrier Proteins; D015342:DNA Probes; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin