当前位置： SCI文献检索 > BLOOD期刊下所有文献 > Interstitial insertion of retinoic acid receptor-alpha gene in acute promyelocytic leukemia with normal chromosomes 15 and 17.

Interstitial insertion of retinoic acid receptor-alpha gene in acute promyelocytic leukemia with normal chromosomes 15 and 17.

Abstract：

:The translocation t(15;17)(q22;q21) is seen exclusively in patients with acute promyelocytic leukemia (APL) and in the promyelocytic blast crisis of chronic myeloid leukemia (CML). This translocation juxta-poses the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor-alpha (RARA) gene on chromosome 17, resulting in the formation of a chimeric mRNA transcript. We describe a patient with the microgranular variant form of APL, with no detectable cytogenetic abnormality of either chromosomes 15 or 17, who nevertheless had juxtaposition of PML and RARA genes and expressed a chimeric transcript. Conventional cytogenetics showed the karyotype 46,XY,d-er(3)t(3;8)(p25;q12). Fluorescent in situ hybridization (FISH) with paints for chromosomes 8, 15, and 17 confirmed the presence of structurally intact chromosomes 15 and 17 and trisomy for chromosome 8q. Nevertheless, FISH using cosmid probes for PML and RARA showed their juxtaposition on one chromosome 15 homolog. Both genes were also present on their normal homologs; in addition, part of the RARA gene was still present on the remaining chromosome 17. DNA analysis by Southern blotting, performed with a variety of probes including PML, RARA and retinoic acid receptor-beta (RARB), showed a rearrangement in PML. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the existence of hybrid transcripts of 276, 455 bp and 623 bp, from PML-RARA on the der(15) chromosome, consistent with alternate exon splicing of the long form of the transcript occurring in 50% to 60% of patients with APL. Our results show that APL patients with cytogenetically normal chromosomes 15 and 17 may, nevertheless, have involvement of both PML and RARA genes defining a subgroup of APL, t(15;17)-negative/PML-RARA-positive which is analogous to Philadelphia chromosome-negative/BCR-ABL-positive CML. In this case, the presence of chimeric transcripts suggests that treatment with all-trans RA may be warranted in APL, even in the absence of detectable cytogenetic change, showing the usefulness of RT-PCR or FISH to aid diagnosis.

journal_name

Blood

journal_title

Blood

authors

Hiorns LR,Min T,Swansbury GJ,Zelent A,Dyer MJ,Catovsky D

subject

Has Abstract

pub_date

1994-05-15 00:00:00

pages

2946-51

issue

eissn

0006-4971

issn

1528-0020

journal_volume

pub_type

杂志文章

在线工具

Interstitial insertion of retinoic acid receptor-alpha gene in acute promyelocytic leukemia with normal chromosomes 15 and 17.