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ABSTRACT: DNA studies of the translocation t(15;17) in acute promyelocytic leukemia (APL) have shown that the retinoic acid receptor alpha (RARA) gene on chromosome 17 is juxtaposed to the promyelocytic leukemia (PML) gene on chromosome 15. The PML breakpoints have been mapped to 3 clusters: bcr1, bcr2, and bcr3. We have examined the PML breakpoint distribution in a series of 33 Chinese patients with APL. Twenty-two patients fell within bcr1, 2 within bcr2, and 9 within bcr3. The primary structure of the reciprocal chromosome translocation joints of one patient and that of their normal counterparts have been determined and compared to those of 2 previously reported cases. These studies revealed possible topoisomerase II cleavage sites close to the breakpoints and suggested implications of DNA attachment sites to nuclear matrix. We propose that these features are relevant to the process of illegitimate recombination generating the translocation.
Genes Chromosomes and Cancer 04/1993; 6(3):133-9. · 3.31 Impact Factor
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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.
Leukemia 02/1993; 7(1):20-6. · 9.56 Impact Factor
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ABSTRACT: Genomic DNA probes generated from the retinoic acid receptor alpha (RARA) gene located on chromosome 17 and from the MYL gene located on chromosome 15 were used to study the chromosome 15 breakpoints resulting from the t(15; 17) translocation in 26 patients with acute promyelocytic leukemia (APL). In 20 out of 22 patients with a detectable MYL rearrangement, the breakpoints were clustered within a 4.4 kb segment designated MYLbcr. The two remaining patients exhibited a more 5' rearrangement at about 10 kb upstream of the MYLbcr region, implying the lack of at least one MYL gene exon in the resulting MYL-RARA fusion gene. The variation of chromosome breakpoints within the MYL gene may explain size heterogeneity previously observed in some MYL-RARA fusion transcripts expressed in APL cells.
Oncogene 03/1992; 7(2):311-6. · 6.37 Impact Factor
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ABSTRACT: The t(15;17)(q22;q11-q21) translocation, a hallmark for acute promyelocytic leukemia (APL), has recently been shown to disrupt the retinoic acid-alpha receptor (RARA) gene localized on band 17q21. Leukemic cell DNAs from 16 Chinese patients with APL were analysed by Southern blot hybridization with probes covering the 5' and the 3' parts of the gene. In ten patients, the breakpoints were concentrated within a 5.5 kb EcoRI fragment containing part of intron 1, whereas no rearrangement was detected in the six remaining patients. Genomic amplification of the RARA gene was observed in one case. When RNA was available (six patients), abnormal-sized RARA gene transcripts were observed. Interestingly, no rearranged transcript was found in cells from a patient during a 6-day treatment with all-trans retinoic acid, while bone marrow cells still possessed the translocation.
Leukemia 05/1991; 5(4):288-92. · 9.56 Impact Factor
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ABSTRACT: The configuration of the P53 tumor suppressor gene was investigated in 43 Chinese patients with chronic myelogenous leukemia (CML), 32 in chronic phase and 11 in blastic crisis. No obvious rearranged DNA band was detected in Southern blot patterns from patients at both stages of the disease. However, P53 gene deletion events were observed in 4 out of 11 cases in blast crisis. This finding was associated with a cytogenetically identifiable chromosome 17p deletion, iso(17q), in only one out of 4 cases.
Nouvelle revue française d'hématologie 02/1991; 33(6):481-4.
