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    BIOMARKER:

    BCR-ABL1 V299L

    i
    Other names: BCR, BCR Activator Of RhoGEF And GTPase, BCR, RhoGEF And GTPase Activating Protein, Breakpoint Cluster Region Protein, Renal Carcinoma Antigen NY-REN-26, Breakpoint Cluster Region, D22S11, BCR1, BCR/FGFR1 Chimera Protein, FGFR1/BCR Chimera Protein, D22S662, ALL, CML, PHL, ABL proto-oncogene 1, ABL, c-ABL, JTK7, p150, ABL1
    Entrez ID:
    25; 613
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    over1year
    Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2023 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK3 (Janus Kinase 3) • CSF1R (Colony stimulating factor 1 receptor) • TSLP (Thymic Stromal Lymphopoietin)
    |
    BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 Q252H • BCR-ABL1 F317V • JAK3 mutation • ABL1 E255K • BCR-ABL1 F317C • BCR-ABL1 T315A • ABL1 F317L • BCR-ABL1 L248R
    |
    dasatinib • Jakafi (ruxolitinib) • dexamethasone
    over1year
    UPDATED RESULTS FROM THE TRIAL ITCC-054/COG-AAML1921: BOSUTINIB IN NEWLY DIAGNOSED AND RESISTANT/INTOLERANT PEDIATRIC PATIENTS WITH CHRONIC MYELOID LEUKEMIA (EHA 2023)
    Bosutinib at the RP2D was well-tolerated and its preliminary efficacy in R/I and ND pediatric patients seems comparable to that recorded in adult patients treated with the same drug and in line with other second generation TKIs. Pediatric, Chronic myeloid leukemia, Clinical trial
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 V299L • ABL1 T315I • BCR-ABL1 mutation
    |
    Bosulif (bosutinib)
    over2years
    PONATINIB IN A REAL-LIFE SETTING: A RETROSPECTIVE ANALYSIS FROM THE MONITORING REGISTRIES OF THE ITALIAN MEDICINES AGENCY (AIFA) (EHA 2022)
    The probability of treatment discontinuation did not significantly differ for ponatinib in second, third or subsequent line of therapy (p=0.58). Conclusion This real-life investigation shows that ponatinib dose reductions were mainly performed in the absence of reported toxicity rather than owing to the occurrence of adverse reactions.
    Retrospective data
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • BCR-ABL1 Y253H • ABL1 T315I • ABL1 E255K • ABL1 F317L • ABL1 Y253H
    |
    Iclusig (ponatinib)
    3years
    A Phase I/II Study of Bosutinib in Pediatric Patients with Resistant/Intolerant or Newly Diagnosed Philadelphia Chromosome-Positive Chronic Myeloid Leukemia, Study ITCC (Innovative Therapies for Children with Cancer European Consortium) 054 and COG (Children's Oncology Group Consortium) AAML1921: Results from the Phase I Trial in Resistant/Intolerant Patients (ASH 2021)
    Its toxicity profile differs from other TKIs approved in children (imatinib, dasatinib and nilotinib), showing a higher incidence of gastrointestinal (GI) adverse events (AEs) but fewer toxicities such as musculoskeletal AEs (Cortes JE et al, 2016). GI toxicities were the most common, mainly during the first cycles and tended to improve in subsequent cycles. Cumulative MMR and CCyR rates were comparable to those reported in literature for other TKIs (Hijiya N et al, 2019).
    Clinical • P1/2 data
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 V299L • ABL1 T315I • BCR-ABL1 mutation
    |
    dasatinib • imatinib • Tasigna (nilotinib) • Bosulif (bosutinib)
    3years
    Efficacy and Safety Results from Ascembl, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, Vs Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase after ≥2 Prior Tyrosine Kinase Inhibitors: Update after 48 Weeks (ASH 2021)
    Resistant/intolerant CML-CP after 2 lines of TKI treatment remains BCR-ABL1 dependent. The novel STAMP inhibitor asciminib demonstrates continued superior efficacy and a limited adverse event profile; myelosuppression, while more prominent, appears to be early and disease related. Secondary resistance based on loss of MMR is rare.
    Clinical • P3 data
    |
    BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 V299L • ABL1 T315I
    |
    Bosulif (bosutinib) • Scemblix (asciminib)
    over3years
    Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023
    Clinical • Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK3 (Janus Kinase 3) • CSF1R (Colony stimulating factor 1 receptor) • TSLP (Thymic Stromal Lymphopoietin)
    |
    BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 Q252H • BCR-ABL1 F317V • JAK3 mutation • ABL1 E255K • BCR-ABL1 F317C • BCR-ABL1 T315A • ABL1 F317L • BCR-ABL1 L248R
    |
    dasatinib • Jakafi (ruxolitinib) • dexamethasone
    almost4years
    FINESTdm: Evaluating Efficacy and Safety of Flumatinib Versus Nilotinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning,Failure) to Imatinib or Dasatinib (clinicaltrials.gov)
    P, N=200, Recruiting, Wuhan Union Hospital, China
    Clinical • New trial
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 V299L • BCR-ABL1 F317L • BCR-ABL1 M244V • BCR-ABL1 M351T • BCR-ABL1 H396R • BCR-ABL1 Q252H • BCR-ABL1 mutation • BCR-ABL1 E355G • BCR-ABL1 L387M • ABL1 F317L • ABL1 L387M • ABL1 M351T
    |
    dasatinib • imatinib • Tasigna (nilotinib) • Hansoh Xinfu (flumatinib)
    4years
    [VIRTUAL] Long-Term Outcome of Chronic Phase Chronic Myeloid Leukemia Patients Treated with Nilotinib Front-Line (ASH 2020)
    Nilotinib (NIL) 600 mg daily has demonstrated its superiority over Imatinib 400 mg daily in terms of response and incidence of deep molecular response in the front-line chronic phase (CP) CML setting...NIL first-line efficiently limits progression of newly diagnosed CP-CML patients and provides high rates of sustained MR4.5, allowing TFR in a substantial proportion of pts. However, the onset of arterial occlusive events, especially in the elderly is a matter of concern in the choice of this compound at treatment initiation.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1)
    |
    BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 Y253H • BCR-ABL1 G250E • BCR-ABL1 M244V • ABL1 T315I • ABL1 E255K • ABL1 F359V • ABL1 G250E • ABL1 Y253H • BCR-ABL1 F359
    |
    imatinib • Tasigna (nilotinib)
    almost5years
    Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Jun 2020 --> Jun 2021
    Clinical • Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK3 (Janus Kinase 3) • CSF1R (Colony stimulating factor 1 receptor) • TSLP (Thymic Stromal Lymphopoietin)
    |
    BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 Q252H • BCR-ABL1 F317V • JAK3 mutation • ABL1 E255K • BCR-ABL1 F317C • BCR-ABL1 T315A • ABL1 F317L • BCR-ABL1 L248R
    |
    dasatinib • Jakafi (ruxolitinib) • dexamethasone