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    BIOMARKER:

    RARA positive

    i
    Other names: 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 Alpha Variant 1, Retinoic Acid Nuclear Receptor Alpha Variant 2, Retinoic Acid Receptor, Alpha Polypeptide, Retinoic Acid Receptor, Alpha, RAR
    Entrez ID:
    5914
    Related biomarkers:
    Expression
    Fusion
    Others
    almost2years
    SY-1425-202: Tamibarotene Plus Venetoclax/Azacitidine in Participants With Newly Diagnosed AML (clinicaltrials.gov)
    P2, N=95, Recruiting, Syros Pharmaceuticals | Trial completion date: Apr 2024 --> Apr 2028 | Trial primary completion date: Apr 2024 --> Apr 2028
    Trial completion date • Trial primary completion date • Combination therapy
    |
    RARA positive
    |
    Venclexta (venetoclax) • azacitidine • Amnolake (tamibarotene)
    almost2years
    SELECT MDS-1: Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome (clinicaltrials.gov)
    P3, N=550, Recruiting, Syros Pharmaceuticals | Trial primary completion date: Dec 2023 --> Nov 2024
    Trial primary completion date
    |
    RARA positive
    |
    azacitidine • Amnolake (tamibarotene)
    over2years
    STAT5B-RARa Fusion Positive Variant Acute Promyelocytic Leukemia: Role of Next-Generation Sequencing in Detection of a Rare Malignancy (AMP Europe 2023)
    The patient received ATO, steroid, and azacytidine; however, within 7 days he developed respiratory distress followed by cardiac arrest which proved fatal... STAT5B-RARa t(17;17) is a rare variant of APML. It exhibits diagnostic, therapeutic, and prognostic difference with the common PML-RARa positive APL and, hence, the need for its prompt identification. Our case demonstrates the valuable role of NGS in reaching a definite diagnosis of such challenging and rare malignancy.
    Next-generation sequencing
    |
    BCR (BCR Activator Of RhoGEF And GTPase) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD33 (CD33 Molecule) • PML (Promyelocytic Leukemia) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • GATA2 (GATA Binding Protein 2) • ANPEP (Alanyl Aminopeptidase, Membrane) • MPO (Myeloperoxidase)
    |
    STAT5b-RARA fusion • RARA positive
    |
    Oncomine Myeloid Assay GX
    |
    azacitidine
    over2years
    Factors associated with thrombo-hemorrhagic deaths in patients with Acute Promyelocytic Leukemia treated with Arsenic Trioxide and All-Trans Retinoic Acid (ISTH 2023)
    The induction and consolidation therapy was with Arsenic Trioxide and All-trans Retinoic Acid without chemotherapy (except hydroxyurea). The median age of 248 patients (140 males, 108 females) was 32 years (Range- 12-73). Two hundred (80.6%) patients had bleeding at presentation. The most common site of bleeding was epistaxis/gum bleed (N=128; 51.6%)(Figure 1).
    Clinical
    |
    RARA (Retinoic Acid Receptor Alpha)
    |
    RARA positive
    |
    arsenic trioxide • hydroxyurea
    over2years
    AML AND MDS WITH RARA OVEREXPRESSION: MOLECULAR AND CLINICAL FEATURES OF PATIENTS ENROLLED IN A PHASE 2 TRIAL EVALUATING TAMIBAROTENE-BASED THERAPY (EHA 2023)
    AML and MDS with RARA overexpression present with molecular features similar to those described in published datasets. Notably, SRSF2 was the most common mutation in the ND older unfit AML cohort, consistent withpublished series. While the small number of RARA -positive MDS patients precludes definitive characterization of molecular profiles, data in AML patients suggest that RARA overexpression may be agnostic to known molecular features.
    P2 data • Clinical
    |
    TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • RARA (Retinoic Acid Receptor Alpha) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2)
    |
    SRSF2 mutation • U2AF1 mutation • RARA overexpression • RARA positive
    |
    Oncomine Myeloid Assay GX
    |
    Venclexta (venetoclax) • azacitidine • Amnolake (tamibarotene)
    over2years
    Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children-A Single Center Experience. (PubMed, Genes (Basel))
    These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation.
    Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • SEPTIN6 (Septin 6) • TBL1XR1 (TBL1X Receptor 1)
    |
    NPM1 mutation • Chr t(15;17) • RARA positive
    almost3years
    Targeting RARA Overexpression with Tamibarotene, a Potent and Selective RARα Agonist, is a Novel Approach in AML. (PubMed, Blood Adv)
    The combination of oral tamibarotene plus azacitidine was evaluated in a Phase 2 clinical study in 51 newly diagnosed unfit AML patients identified as RARA-positive (N = 22) or RARA-negative (N = 29) for RARA mRNA overexpression in peripheral blasts with a blood-based biomarker test. These results support further evaluation of tamibarotene-based treatment strategies in AML and MDS patients with RARA overexpression to provide a targeted approach with the goal of improving patient outcomes. This trial is registered at www.clinicaltrials.gov as NCT02807558.
    Journal
    |
    RARA (Retinoic Acid Receptor Alpha)
    |
    RARA overexpression • RARA positive
    |
    azacitidine • Amnolake (tamibarotene)