APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RARa gene on chromosome 17 and gives rise to the PML/RARa fusion protein.
Secondly, the 15;17 chromosomal translocation specific for APL leads at the molecular genetic level to a chimeric gene fusing the PML and RAR alpha genes and appears to be an instrumental, if not actually the causative event, in the neoplastic process.
Acute promyelocytic leukemia (APL; M3 in the FAB classification) is specifically associated with the t(15;17)(q23;q12) and the consequent formation of a PML/RARA fusion gene.
APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RAR alpha gene on chromosome 17 and gives rise to the PML/RAR alpha fusion protein.
Molecular analysis of the t(15;17) translocation in 70 patients with acute promyelocytic leukemia (APL) confirmed that the breakpoints of chromosome 15 were located in two regions of the promyelocytic leukemia (PML) gene, mainly introns 3 and 6, whereas the breakpoints of chromosome 17 were consistently in intron 2 of the retinoic acid receptor alpha (RARA) gene.
The t(15;17) chromosomal translocation, specific for acute promyelocytic leukemia (APL), fuses the PML gene to the retinoic acid receptor alpha (RAR alpha) gene, resulting in expression of a PML-RAR alpha hybrid protein.
Prognostic significance of the RT-PCR assay of PML-RARA transcripts in acute promyelocytic leukemia. The Leukemia Study Group of the Ministry of Health and Welfare (Kouseisho).
We and others have shown that the t(15;17) translocation specifically associated with APL fuses an as yet unidentified gene, named PML, to the retinoic acid receptor alpha locus.
Southern genomic analysis demonstrated re-arrangements of the retinoic acid receptor varies; is directly proportional to (RAR varies; is directly proportional to) and PML genes in the APL blasts at presentation but not in the M2 ANLL marrow at relapse.
The acute promyelocytic leukemia (APL)-specific t(15;17) chromosome abnormality is characterized at the molecular level by rearrangement of the PML and RAR alpha genes, resulting in fusion PML/RAR alpha mRNA and a chimeric protein.
The PML gene located on chromosome band 15q22 is involved with the RAR alpha locus (17q21) in a balanced reciprocal translocation uniquely observed in acute promyelocytic leukemia.
PML is normally a component of a nuclear multiprotein complex (termed ND10, Kr bodies, nuclear bodies, PML oncogenic domains or PODs) which is disrupted in the APL disease state.
This study supports our hypothesis that disruption of the normal function of PML, a growth or transformation suppressor, is a critical event in APL leukomogenesis.
Promyelocytic leukemia-specific PML-retinoic acid alpha receptor fusion protein interferes with erythroid differentiation of human erythroleukemia K562 cells.
Acute promyelocytic leukemia (APL) is characterized by a unique hemorrhagic syndrome, disseminated intravascular coagulation, and the association with the specific (15;17 chi q22-23:q12-21) translocation, which disrupts the retinoic acid receptor alpha (RARA) and the promyelocytic leukemia (PML) genes.
In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins.
Although parallel assessment of PML-RAR alpha and RAR alpha-PML can enhance minimal residual disease detection in APL, this study demonstrates that treatment strategies involving determination of PCR status post-consolidation, even using RAR alpha-PML in addition to the more conventional PML-RAR alpha assay will fail to identify all patients at risk of relapse.
We demonstrate that mutants in both B1 and B2 do not form PML nuclear bodies in vivo and have a phenotype that is different from that observed in the APL disease state.