Korean J Clin Pathol.  1997 Dec;17(6):885-897.

The t (15;17) Breakpoint of the PML Gene in Acute Promyelocytic Leukemia

• Park SS
• Cho HI

Abstract

BACKGROUND: The characteristic t(15; 17) of acute promyelocytic leukemia (APL) fuses the retinoic acid receptor alpha (RARA) gene on chromosome 17 to the PML gene on chromosome 15. The test of PML-RARA rearrangement is essential for diagnosis and therapy of APL. We analyzed breakpoints of the PML gene as a basic study for PML-RARA rearrangement test.
METHODS
PML-RARA rearrangements, breakpoints of the PML gene and junction sequences were analyzed in 41 patients with APL using RT-PCR and direct sequencing.
RESULTS
Forty out of 41 cases revealed PML-RARA rearrangement, of which results coincided with cytogenetic data. Breakpoint distribution was 26 cases in burl (65%), one in bcr2 (2.5%), and 13 in bcr3 (32.5%). Sequencing data showed invariable joining of exon 3 of the RARA gene and exon 6 (bcrl type) or exon 3 (bcr3 type) of the PML gene. One case with bcr2 type had breakpoint in exon 6 of the PML gene with 57 bp deletion.
CONCLUSIONS
Bcrl Is the most common breakpoint site of APL in Koreans, and bcy1+2/bcr3 ratio is approximately 2.1. PML-RARA junctions were continuous and joined by a correct splicing event. Breakpoint analysis would be useful in quality control of PML-RARA rearrangement test and the fused protein analysis.

MeSH Terms

Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 17
Cytogenetics
Diagnosis
Exons
Humans
Leukemia, Promyelocytic, Acute*
Quality Control
Receptors, Retinoic Acid
Receptors, Retinoic Acid