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    BIOMARKER:

    PML-RARA A216V

    i
    Other names: PML, Promyelocytic Leukemia, Tripartite Motif-Containing Protein 19, Promyelocytic Leukemia Protein, RING Finger Protein 71, Protein PML, PP8675, TRIM19, RNF71, MYL, Promyelocytic Leukemia, Inducer Of, Probable Transcription Factor PML, Tripartite Motif Protein TRIM19, PML/RARA Fusion, RARA, Retinoic Acid Receptor Alpha, Nuclear Receptor Subfamily 1 Group B Member 1, RAR-Alpha, NR1B1, Nucleophosmin-Retinoic Acid Receptor Alpha Fusion Protein NPM-RAR Long Form, Retinoic Acid Nuclear Receptor Alph
    Entrez ID:
    5914; 5371
    Related biomarkers:
    Expression
    Fusion
    Others
    Associations

    News

    Trials
    5ms
    Mutations at proximal cysteine residues in PML impair ATO binding by destabilizing the RBCC domain. (PubMed, FEBS J)
    Acute promyelocytic leukemia (APL) is characterized by the fusion gene promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) and is conventionally treated with arsenic trioxide (ATO)...In addition, these mutations disrupt several hydrogen bonds, including interactions involving C212, C213 and C215, which are essential for ATO binding. The local and global structural features induced by these mutations provide mechanistic insight into ATO resistance and APL pathogenesis.
    Journal
    |
    RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)
    |
    PML-RARA A216V • PML-RARA L218P
    |
    arsenic trioxide
    9ms
    Venetoclax Upregulates Mitochondrial Stress Response to Overcome the Resistance to Arsenic Trioxide in Acute Promyelocytic Leukemia (SOHO 2023)
    Immunoblotting confirmed that ATO-resistant cells were unable to undergo apoptosis as levels of pro-apoptotic (cleaved caspase-3, cleaved-PARP, BAX), anti-apoptotic (Bcl2, Bcl-xL, XIAP), and PML-RARA proteins remain unchanged in ATO-resistant cells except for downregulation of Bcl2 and upregulation of cleaved caspase-3 in UF1 following ATO/ATRA treatment. Our results indicate that venetoclax+ATO cooperates in inducing apoptosis of ATO-resistant cells through mitochondrial stress-induced ROS production coupled with PML-RARA degradation.
    PARP Biomarker • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • PML (Promyelocytic Leukemia) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CASP3 (Caspase 3) • XIAP (X-Linked Inhibitor Of Apoptosis)
    |
    PML-RARA A216V
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    Venclexta (venetoclax) • Vesanoid (tretinoin) • arsenic trioxide