Acute promyelocytic leukemia and variant fusion proteins: PLZF-RARα fusion protein at a glance.

@article{Hussain2019AcutePL,
  title={Acute promyelocytic leukemia and variant fusion proteins: PLZF-RAR$\alpha$ fusion protein at a glance.},
  author={Liaqat Hussain and Yasen Maimaitiyiming and Khairul Islam and Hua Naranmandura},
  journal={Seminars in oncology},
  year={2019}
}
Classical acute promyelocytic leukemia (APL) cases are associated with the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) chimeric fusion protein. Almost all the variant chimeric proteins share the same RARα component. Currently, more than 11 fusion partners of RARα have been identified, of which PML accounts for 95%, promyelocytic leukemia zinc finger (PLZF) take up2%, and the remaining are other variants. Although all-trans retinoic acid and arsenic trioxide have shown remarkable… Expand
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References

SHOWING 1-10 OF 109 REFERENCES
Acute promyelocytic leukemia with a PLZF-RARα fusion protein
TLDR
Targeting of the PLZF-RARalpha-bound corepressor complexes using a combination of all-trans retinoic acid (ATRA) and deacetylase inhibitors has shown that the repression of target genes can be relieved, allowing differentiation of the cells. Expand
The RARα-PLZF chimera associated with Acute Promyelocytic Leukemia has retained a sequence-specific DNA-binding domain
TLDR
The hypothesis that RARα-PLZF chimera is not an inert product of reciprocal translocation and may thus contribute to ATRA unresponsiveness of t(11;17)-associated APL is supported. Expand
Targeting the Acute Promyelocytic Leukemia-Associated Fusion Proteins PML/RARα and PLZF/RARα with Interfering Peptides
TLDR
Specific interfering polypeptides were used to target the oligomerization domain of PML/RARα or PLZF-induced high-molecular-weight complex formation and caused the degradation of the fusion protein. Expand
Identification of a novel fusion gene, IRF2BP2-RARA, in acute promyelocytic leukemia.
TLDR
This report presents a patient with APL with a novel fusion between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2) genes, and it expands the list of novel RARA partners identified in APL. Expand
RARA fusion genes in acute promyelocytic leukemia: a review
TLDR
RARA fusion proteins behave as potent transcriptional repressors of retinoic acid signalling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of ATRA or arsenic trioxide, but resistance to these two drugs is a major problem, which necessitates development of new therapies. Expand
Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia
TLDR
The hypothesis that while deregulation of both the retinoid signaling pathway and RARα partner proteins are molecular consequences of APL translocations, APL pathogenesis is not dependent on disruption of PML nuclear bodies is supported. Expand
Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia.
TLDR
It appears that N-CoR/histone deacetylase corepressor complex interacts directly in an ATRA-insensitive manner with the BTB/POZ-domain of the wild-type PLZF protein and is required, at least in part, for its function as a transcriptional repressor. Expand
BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia.
TLDR
A novel RARA fusion transcript, BCOR-RARA, is identified in a t(X;17)(p11;q12) variant of APL with unique morphologic features, including rectangular and round cytoplasmic inclusion bodies, which highlight essential features of pathogenesis in APL in more detail. Expand
Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia
TLDR
It is shown that both PML–RARα and PLZF–Rarα fusion proteins recruit the nuclear co-repressor (N-CoR)–histone deacetylase complex through the RARα CoR box, which determines the differential response of APLs to RA. Expand
Fusion of retinoic acid receptor α to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia
TLDR
It is suggested that interference with retinoid signalling, and not disruption of PML organization, is essential to the APL phenotype and implicates for the first time an element of the mitotic apparatus in the molecular pathogenesis of human malignancy. Expand
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