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    BIOMARKER:

    CXCR4 S338X

    i
    Other names: CXCR4, CD184, D2S201E, fusin, HM89, HSY3RR, LESTR, NPY3R, NPYR, NPYY3R, Chemokine (C-X-C motif) receptor 4
    Entrez ID:
    7852
    Related biomarkers:
    Expression
    Mutation
    10ms
    How we use Genomics and BTK-Inhibitors in the Treatment of Waldenstrom Macroglobulinemia. (PubMed, Blood)
    The cBTK-i zanubrutinib shows greater response activity and/or improved PFS in wild-type MYD88, mutated CXCR4, or altered TP53 patients...For patients with acquired resistance to c-BTKi, newer options include the non-covalent BTK-inhibitor pirtobrutinib or the BCL2 antagonist venetoclax. Combinations of BTK-inhibitors with chemoimmunotherapy, CXCR4 and BCL2 antagonists have advanced and are discussed. Algorithms for positioning BTK-inhibitors in treatment-naïve and previously treated WM patients based on genomics, disease characteristics, and co-morbidities are presented.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    TP53 mutation • MYD88 mutation • CXCR4 mutation • MYD88 mutation + CXCR4 mutation • CXCR4 S338X • MYD88 wild-type
    |
    Venclexta (venetoclax) • Brukinsa (zanubrutinib) • Jaypirca (pirtobrutinib)
    12ms
    CXCR4 S338X Promotes Resistance to Second Generation BTK Inhibitor and BCL-2 Inhibitor in WM Cells (ASH 2023)
    The aim of this study was to further investigate the effect of CXCR4 S338X on BTK inhibitors (ibrutinib and zanubrutinib) and a BCL-2 inhibitor (venetoclax) resistance. The above data demonstrate the role of CXCR4 S338X mutation in drug resistance and suggest the necessity to develop therapeutic strategies to address this issue and overcome this therapeutic barrier in WM. Data on more cell lines and downstream signaling will be presented at the meeting.
    IO biomarker
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • ANXA5 (Annexin A5)
    |
    MYD88 L265P • CXCR4 mutation • CXCR4 S338X • CXCR4 expression
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
    over1year
    FIL_BIOWM: Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS (clinicaltrials.gov)
    P=N/A, N=300, Active, not recruiting, Fondazione Italiana Linfomi ONLUS | Trial completion date: Dec 2022 --> Oct 2025
    Trial completion date • Minimal residual disease
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 mutation • MYD88 L265P • CXCR4 S338X
    over1year
    Waldenström macroglobulinemia and non-IgM-type lymphoplasmacytic lymphoma are genetically similar. (PubMed, Acta Haematol)
    Most mutations detected by NGS were subclonal following MYD88 L265P, although one non-IgM-type LPL patient harbored only CXCR4 S338X mutation. Our NGS analyses reveal genetic characteristics in LPL patients and suggest genetic similarities between these two subsets of LPL, WM and non-IgM-type.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • PRDM1 (PR/SET Domain 1)
    |
    TP53 mutation • ARID1A mutation • KMT2D mutation • MYD88 L265P • CXCR4 mutation • CD79B mutation • CXCR4 S338X • MYD88 L265P + CXCR4 mutation
    over2years
    A NOVEL DROP-OFF DIGITAL PCR ASSAY FOR CXCR4 MUTATION SCREENING IN IGM GAMMOPATHIES: FIRST DATA FROM THE FONDAZIONE ITALIANA LINFOMI BIO-WM STUDY (EHA 2022)
    A statistically significant difference in CXCR4 MUT level was observed between patients treated at the time of enrollment and those still in WW. However, a longer FU is needed to better clarify the clinical implications of CXCR4 mutations in our series.
    Tumor Mutational Burden
    |
    TMB (Tumor Mutational Burden) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD19 (CD19 Molecule) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 L265P • CXCR4 mutation • CD19 mutation • CXCR4 S338X
    almost3years
    FIL_BIOWM: Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS (clinicaltrials.gov)
    P=N/A, N=300, Active, not recruiting, Fondazione Italiana Linfomi ONLUS | Trial completion date: Mar 2022 --> Dec 2022
    Trial completion date • Minimal residual disease
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 mutation • MYD88 L265P • CXCR4 S338X
    over3years
    FIL_BIOWM: Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS (clinicaltrials.gov)
    P=N/A, N=300, Active, not recruiting, Fondazione Italiana Linfomi ONLUS | Trial primary completion date: Jun 2021 --> Oct 2020
    Trial primary completion date • Minimal residual disease
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 mutation • MYD88 L265P • CXCR4 S338X
    over3years
    FIL_BIOWM: Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS (clinicaltrials.gov)
    P=N/A, N=300, Active, not recruiting, Fondazione Italiana Linfomi ONLUS | Recruiting --> Active, not recruiting
    Enrollment closed • Minimal residual disease
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 mutation • MYD88 L265P • CXCR4 S338X
    over3years
    Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next-generation sequencing in Waldenström macroglobulinaemia. (PubMed, Br J Haematol)
    Both CD19 selection and AS-PCR markedly improved detection of CXCR4 mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality.
    Journal • Next-generation sequencing
    |
    CD19 (CD19 Molecule) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    CXCR4 mutation • CXCR4 S338X
    |
    Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)