Localization of the chromosome 15 breakpoints and expression of multiple PML-RAR alpha transcripts in acute promyelocytic leukemia: a study of 28 Chinese patients

Abstract

Translocation (15;17)(q22;q12-q21) is a chromosome aberration specifically found in acute promyelocytic leukemia (APL), that generates a chimeric gene between the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARA) gene, on chromosome 17. In the course of molecular investigations of a series of 28 Chinese patients with APL, we have simultaneously used Southern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analysis to characterize the PML gene breakpoints on chromosome 15 and identify PML-RARA fusion transcripts. Our results confirmed the existence of the three recently described bcr1, bcr2, and bcr3 breakpoint cluster regions. In addition, structural data provided by PML-RARA transcripts allowed us to more accurately locate the 3' borders of clusters bcr1 and bcr3. Moreover, our data suggest a preferential localization of the breakpoints within bcr1 and bcr3. The primary structure of a 1.4 kb DNA segment flanking the 5' part of the PML gene and that of the bcr3 cluster (2.1 kb) were also established.