scholarly journals Retinoic acid receptor-α (RARA); promyelocytic leukemia (PML); histone deacetylase (HDAC)

2014 ◽  
Vol 7 (13) ◽  
pp. 365-365
Keyword(s):  
Retinoic Acid ◽  
Histone Deacetylase ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

Detection of PML-retinoic acid receptor-α fusion transcripts in acute promyelocytic leukemia with trisomy 8 but without t(15;17)

1994 ◽  
Vol 45 (3) ◽  
pp. 212-216 ◽  
Author(s):  
Kazuma Ikeda ◽  
Kazunori Sasaki ◽  
Taizo Tasaka ◽  
Masami Nagai ◽  
Koichi Kawanishi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
Trisomy 8 ◽  
Acid Receptor ◽  
Fusion Transcripts ◽  
Retinoic Acid Receptor Α

Pharicin B, a Novel Diterpenoid, Stabilizes Retinoic Acid Receptor-α Protein and Induces Differentiation of AML Cells in the Presence of Physiological Doses of ATRA.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1601-1601
Author(s):  
Guo-Qiang Chen ◽  
Zhi-Min Gu ◽  
Mei-Yi Zhou ◽  
Ying-Li Wu ◽  
Ying Huang
Keyword(s):  
Retinoic Acid ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Retinoic Acid Receptor ◽  
Chinese Herb ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Dietary Vitamin ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

Abstract Retinoids, a generic term that covers compounds including both naturally dietary vitamin A (retinol) metabolites and active synthetic analogs, exert their pleiotropic effects such as anticancer activity through the three retinoic acid receptors (RARs) subtypes [RARα, RARβ and RARγ]. The most impressive example of retinoid anticancer activity is the successful application of all-trans retinoic acid (ATRA) in the treatment of patients with acute promyelocytic leukemia (APL), a unique subtype of acute myelogenous leukemia (AML) which characterized with the specific reciprocal chromosome translocation t(15;17) that results in the expression of leukemia-promoting promyelocytic leukemia-retinoic acid receptor-α (PML-RARα) chimeric protein. However, retinoid resistance frequently occurred in ATRA-treated patients. Isodon xerophilus, a perennial shrub native to Southern China, has been used as an anti-tumor, anti-inflammatory, and anti-microbial agent in Chinese herb medicine for a long history. During the past 30 years, a large number of ent-kauranoids have been isolated from the genus Isodon, many of which exhibit potent antitumor activities with a relatively low toxicity. In this work, we identified a novel ent-kaurene diterpenoid named pharicin B to rapidly stabilize RARα as well as PML-RARα protein in AML cell lines. More intriguingly, it also antagonizes ATRA-induced degradation of RARα and PML-RARα proteins. The interesting finding promotes us to investigate its possible effects on AML cells. Our results demonstrated that pharicin B at nontoxic concentration suppresses growth in APL cell line NB4 and myeloblactic leukemic U937 and THP-1 cell lines. Together with exceedingly low concentration of ATRA and RARα specific agonist AM580 existed, pharicin B significantly triggered all the three cell lines and some NB4-derived ATRA-resistant cell lines such as NB4-MR2 and NB4-LR1 (but not NB4-LR2) to undergo myeloid maturation, as evidenced by morphology, CD11/CD14 expression and NBT reduction test. All these results proposed that pharicin B would be a good tool for investigating mechanisms of RARα stabilization and degradation induced by ATRA as well as retinoid resistance, and its combination with ATRA might present the clinical potentials for differentiation-inducing therapy of APL and other AML patients.

scholarly journals Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation

2001 ◽  
Vol 193 (12) ◽  
pp. 1361-1372 ◽  
Author(s):  
Valérie Lallemand-Breitenbach ◽  
Jun Zhu ◽  
Francine Puvion ◽  
Marcel Koken ◽  
Nicole Honoré ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Matrix ◽  
Viral Infections ◽  
Retinoic Acid Receptor ◽  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Acid Receptor ◽  
Pml Nuclear Bodies ◽  
Retinoic Acid Receptor Α

Promyelocytic leukemia (PML) is the organizer of nuclear matrix domains, PML nuclear bodies (NBs), with a proposed role in apoptosis control. In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) α expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARα and that this process requires a specific sumolation site in PML, K160. PML sumolation is dispensable for its As2O3-induced matrix targeting and formation of primary nuclear aggregates, but is required for the formation of secondary shell-like NBs. Interestingly, only these mature NBs harbor 11S proteasome components, which are further recruited upon As2O3 exposure. Proteasome recruitment by sumolated PML only likely accounts for the failure of PML-K160R to be degraded. Therefore, studying the basis of As2O3-induced PML/RARα degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation.

scholarly journals Bcl-2 Cooperates with Promyelocytic Leukemia Retinoic Acid Receptor α Chimeric Protein (Pmlrarα) to Block Neutrophil Differentiation and Initiate Acute Leukemia

2001 ◽  
Vol 193 (4) ◽  
pp. 531-544 ◽  
Author(s):  
Scott C. Kogan ◽  
Diane E. Brown ◽  
David B. Shultz ◽  
Bao-Tran H. Truong ◽  
Valerie Lallemand-Breitenbach ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
Transgenic Mice ◽  
Retinoic Acid Receptor ◽  
Chimeric Protein ◽  
Promyelocytic Leukemia ◽  
Chromosome 2 ◽  
Acute Leukemias ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

The promyelocytic leukemia retinoic acid receptor α (PMLRARα) chimeric protein is associated with acute promyelocytic leukemia (APL). PMLRARα transgenic mice develop leukemia only after several months, suggesting that PMLRARα does not by itself confer a fully malignant phenotype. Suppression of apoptosis can have a central role in tumorigenesis; therefore, we assessed whether BCL-2 influenced the ability of PMLRARα to initiate leukemia. Evaluation of preleukemic animals showed that whereas PMLRARα alone modestly altered neutrophil maturation, the combination of PMLRARα and BCL-2 caused a marked accumulation of immature myeloid cells in bone marrow. Leukemias developed more rapidly in mice coexpressing PMLRARα and BCL-2 than in mice expressing PMLRARα alone, and all mice expressing both transgenes succumbed to leukemia by 7 mo. Although both preleukemic, doubly transgenic mice and leukemic animals had abundant promyelocytes in the bone marrow, only leukemic mice exhibited thrombocytopenia and dissemination of immature cells. Recurrent gain of chromosomes 7, 8, 10, and 15 and recurrent loss of chromosome 2 were identified in the leukemias. These chromosomal changes may be responsible for the suppression of normal hematopoiesis and dissemination characteristic of the acute leukemias. Our results indicate that genetic changes that inhibit apoptosis can cooperate with PMLRARα to initiate APL.

Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia

Nature ◽  
10.1038/35901 ◽  
1998 ◽  
Vol 391 (6669) ◽  
pp. 815-818 ◽  
Author(s):  
Francesco Grignani ◽  
Silvia De Matteis ◽  
Clara Nervi ◽  
Lucia Tomassoni ◽  
Vania Gelmetti ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Histone Deacetylase ◽  
Fusion Proteins ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukaemia ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α
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