Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins.
|
10954752 |
2000 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
These data clearly establish the leukemogenic role of PLZF-RARalpha and NPM-RARalpha and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.
|
10339585 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, APL associated with translocation between the RARalpha and the PLZF genes (PLZF-RARalpha) shows a distinctly worse prognosis with poor response to chemotherapy and little or no response to treatment with RA, thus defining a new APL syndrome.
|
10498880 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
Taken together, these data provide novel insights into the mechanisms involved in As2O3-induced apoptosis in APL and predict that treatment of t(11;17) (PLZF-RARalpha-positive) APLs with As2O3 will not be successful.
|
10373566 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
We described previously an APL case with an unbalanced t(5;17) implicating RARA but neither PML nor PLZF.
|
10360373 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
FAZF is homologous to the promyelocytic leukemia zinc finger (PLZF) protein, which has been shown to act as a transcriptional repressor by recruitment of nuclear corepressors (N-CoR, Sin3, and HDAC1 complex).
|
10572087 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Although the vast majority of APLs respond to retinoic acid therapy, those associated with PLZF-RARalpha are resistant.
|
10397747 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia.
|
9989813 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Deregulation of cyclin A2 by RARalpha-PLZF may represent an oncogenic mechanism of this chimeric protein and contribute to the aggressive clinical phenotype of t(11;17)(q23;q21)-associated APL.
|
10023668 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Primary blasts of a t(11;17)(q23;q21) acute promyelocytic leukaemia (APL) patient were analysed with respect to retinoic acid (RA) and arsenic trioxide (As2O3) sensitivity as well as PLZF/RARalpha status.
|
10023688 |
1999 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
Taken together, our results demonstrate involvement of nuclear receptor corepressor/histone deacetylase complex in the molecular pathogenesis of APL and provide an explanation for differential sensitivities of PML- and PLZF-RARalpha-associated leukemias to ATRA.
|
9531570 |
1998 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
We and others have previously implicated the SMRT corepressor in the actions of the PLZF transcription factor and in the function of its oncogenic derivative, PLZF-retinoic acid receptor (RARalpha), in promyelocytic leukemia.
|
9765306 |
1998 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
We have generated PML-RARA and PLZF-RARA transgenic mice and show here that these fusion proteins play a critical role in leukaemogenesis and in determining responses to RA in APL, because PLZF-RARA transgenic mice develop RA-resistant leukaemia, while PML-RARA mice are responsive to RA treatment.
|
9462740 |
1998 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
These results suggest that RARalpha-PLZF, generated in acute promyelocytic leukemia, is an aberrant transcription factor that can deregulate the expression of PLZF target genes and contribute to leukemogenesis.
|
9278395 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia.
|
8952164 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
Their different activities on the RA signalling pathway might underlie the different responses of PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment.
|
9234742 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Although PLZF-RAR alpha and PML-RAR alpha are similar in their apparent dominant negative effects, t(11;17)-associated APL is refractory to ATRA therapy.
|
9070655 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
In 6 of 7 cases, cryptic PML-RARalpha rearrangements were identified by reverse transcriptase-polymerase chain reaction and fluorescent in situ hybridization (FISH); whereas, in the remaining patient, APL was associated with the variant translocation, t(11; 17)(q23; q12-21), leading to the formation of PLZF-RARalpha and RARalpha-PLZF fusion genes.
|
9389704 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia.
|
9256429 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
We further characterized the genomic organization of the promyelocytic leukemia zinc finger (PLZF) gene that maps within the PGL1 critical region and physically excluded the serotonin receptor type 3 (5HT3R) gene.
|
9299238 |
1997 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
Leukemogenesis in t(11;17) APL may be related to interference with ATRA-mediated differentiation due to sequestration of RXR by the PLZF-RAR alpha chimera.
|
8570209 |
1996 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
These different protein-protein interactions and the target gene specificities of PLZF-RARalpha and PML-RARalpha may underlie, at least in part, the apparent resistance of APL with t(11;17) to differentiation effects of all-trans-retinoic acid.
|
8622986 |
1996 |
Acute Promyelocytic Leukemia
|
0.600 |
Biomarker
|
disease |
BEFREE |
Current data suggest that PML-RAR alpha and PLZF-RAR alpha fusion receptors may play an important role in the development of APL and that PML-RAR alpha could be the target of ATRA differentiation therapy.
|
8721678 |
1996 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The RARA sequences are the same as the RARA sequences found in the PML-RAR and PLZF-RAR fusion seen in t(15;17) and t(11;17) APL, respectively.
|
8562957 |
1996 |
Acute Promyelocytic Leukemia
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
A few cases of APL with a t(11;17)(q23;q12) and a PLZF/RARA fusion gene have recently been reported.
|
8605120 |
1995 |