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    BIOMARKER:

    CRLF2 overexpression

    i
    Other names: CRLF2, Cytokine Receptor Like Factor 2, Thymic Stromal Lymphopoietin Protein Receptor, Cytokine Receptor-Like Factor 2, TSLP Receptor, IL-XR, TSLPR, CRL2, Thymic Stromal-Derived Lymphopoietin Receptor, Cytokine Receptor CRL2 Precusor, Cytokine Receptor-Like 2, CRLF2Y, ILXR
    Entrez ID:
    64109
    Related biomarkers:
    Mutation
    Fusion
    Others
    23d
    OUTCOMES IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH DOWN SYNDROME AND ACUTE LYMPHOBLASTIC LEUKEMIA: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP (SIOP 2022)
    Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on HR trials (4.1% vs 1.7%, p = 0.001).ConclusionsPatients with DS B-ALL exhibit increased rates of treatment toxicity, death during treatment, and relapse. Novel therapeutic strategies are needed to improve these outcomes.
    Clinical
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    CRLF2 (Cytokine Receptor Like Factor 2)
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    CRLF2 overexpression
    2ms
    High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia. (PubMed, Cytokine)
    In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS.
    Journal
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    CRLF2 (Cytokine Receptor Like Factor 2) • P2RY8 (P2Y Receptor Family Member 8)
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    CRLF2 rearrangement • CRLF2 overexpression • IGH-CRLF2 fusion
    2ms
    Genetic and Epigenetic Mechanisms Deregulate the CRL2 Complex in Hepatocellular Carcinoma. (PubMed, Front Genet)
    Combining miRNA and mRNA expression, DNA copy number, and methylation status into one multidimensional survival analysis, we found a significant association between greater numbers of alterations and poorer overall survival for multiple component genes. While the intricacies of CRL2 complex gene regulation require additional research, it is evident that multiple causes for the deregulation of these genes must be considered in HCC, including non-traditional mechanisms.
    Journal
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    CRLF2 (Cytokine Receptor Like Factor 2) • MIR139 (MicroRNA 139)
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    CRLF2 overexpression
    2ms
    CRLF2 overexpression defines an immature-like subgroup which is rescued through restoration of the PRC2 function in T-cell precursor acute lymphoblastic leukaemia. (PubMed, Genes Chromosomes Cancer)
    We identified that IKZF1 transcripts with intron retention were upregulated in the CRLF2-high subgroup. Here, we delineated the gene expression profile of CRLF2-high T-ALL samples and unravelled the crucial role of PRC2 in CRLF2 regulation in ETP-ALL.
    Journal
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    PTEN (Phosphatase and tensin homolog) • RUNX1 (RUNX Family Transcription Factor 1) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • JAK3 (Janus Kinase 3) • PHF6 (PHD Finger Protein 6)
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    PTEN mutation • RUNX1 mutation • EZH2 mutation • CRLF2 overexpression • JAK3 mutation • PHF6 mutation
    3ms
    CRLF2 overexpression results in reduced B cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome. (PubMed, Exp Hematol)
    Thus, CRLF2 overexpression results in reduced B cell differentiation and enhanced E2F signaling in Dp16 B-progenitor cells and DS-ALL patient samples. These findings suggest a functional basis for the high frequency of CRLF2-R in DS-ALL as well as a potential therapeutically targetable pathway.
    Preclinical • Journal
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    CRLF2 (Cytokine Receptor Like Factor 2)
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    CRLF2 rearrangement • CRLF2 overexpression
    3ms
    BIMODAL TARGETING OF CYTOKINE RECEPTOR-LIKE FACTOR 2 (CRLF2) WITH JAK INHIBITION AND CHIMERIC ANTIGEN RECEPTOR T CELL IMMUNOTHERAPY IN DOWN SYNDROME ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2022)
    These genetic alterations induce constitutive JAK/STAT and other kinase signaling that may be targetable by the JAK1/2 inhibitor ruxolitinib...These results suggest potential for both anti-ALL efficacy and CRS dampening when JAK inhibition and TSLPRCART are properly time-sequenced and may have broader applicability for toxicity mitigation with other cellular immunotherapies. Studies of CAR T cell immunotherapy and other kinase inhibitors in additional CRLF2 -rearranged and non-rearranged DS-ALL models are ongoing.
    CAR T-Cell Therapy • IO biomarker
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CRLF2 (Cytokine Receptor Like Factor 2) • IL2 (Interleukin 2) • TSLP (Thymic Stromal Lymphopoietin)
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    BCR-ABL1 mutation • CRLF2 rearrangement • CRLF2 overexpression
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    Jakafi (ruxolitinib)