Variant-type PML-RAR fusion transcript in acute promyelocytic leukemia: Use of a cryptic coding sequence from intron 2 of the RAR gene and identification of a new clinical subtype resistant to retinoic acid therapy
نویسندگان
چکیده
*State Key Lab for Medical Genomics and Samuel Waxman Cancer Research Foundation Lab, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Second Medical University, 197 Rui Jin Road II, Shanghai 200025, China; ‡Chinese National Human Genome Center at Shanghai, 351 Guo Shou Jing Road, Pudong, Shanghai 201203, China; §State Key Lab for Genetic Engineering, FuDan University, 220 Han Dan Road, Shanghai 200433, China; ¶Section of Infectious Disease, Department of Medicine, Baylor College of Medicine, Houston, TX 77030; Department of Internal Medicine, University of Texas Medical School, Houston, Texas 77030; and **Department of Oncology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467
منابع مشابه
Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.
A unique mRNA produced in leukemic cells from a t(15;17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor alpha (RAR alpha) and a myeloid gene product called PML. PML contains a cysteine-rich region present in a new family of apparent DNA-binding proteins that includes a regulator of the interleukin-2 receptor gene (Rpt-1) and the recombinat...
متن کاملReverse transcription polymerase chain reaction for the rearranged retinoic acid receptor alpha clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia.
The characteristic t(15;17) of acute promyelocytic leukemia (APL) fuses the retinoic acid receptor alpha (RAR-alpha) gene on chromosome 17 to a gene on chromosome 15 called PML, a putative transcription factor. This distinct translocation results in a fusion mRNA detected by Northern analysis. Two cDNAs have been isolated that differ in the extent of 3' PML nucleic acid sequence contained. This...
متن کاملA PML/retinoic acid receptor alpha fusion transcript is constantly detected by RNA-based polymerase chain reaction in acute promyelocytic leukemia.
The t(15;17) translocation is specifically observed in patients with promyelocytic leukemia (AML3). The chromosomal rearrangement juxtaposes the retinoic acid receptor alpha (RAR alpha) and PML genes, resulting in PML/RAR alpha fusion transcripts. Our previous studies have shown that a polymerase chain reaction (PCR) amplification product could be obtained from the cDNA of the NB4 promyelocytic...
متن کاملThe t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.
We have studied an acute promyelocytic leukemia (APL) patient with a variant t(5;17)(q32;q12). This translocation fuses the gene for the nucleolar phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor alpha (RARA). Two alternatively spliced transcripts are expressed, which differ in 129 bases immediately upstream of the RARA sequence. The NPM sequences contained in the shorter NPM-RA...
متن کاملA retinoid-resistant acute promyelocytic leukemia subclone expresses a dominant negative PML-RAR alpha mutation.
The unique t(15;17) of acute promyelocytic leukemia (APL) fuses the PML gene with the retinoic acid receptor alpha (RAR alpha) gene. Although retinoic acid (RA) inhibits cell growth and induces differentiation in human APL cells, resistance to RA develops both in vitro and in patients. We have developed RA-resistant subclones of the human APL cell line, NB4, whose nuclear extracts display alter...
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