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BIOMARKER:

BCR-ABL1 F317V

i
Entrez ID:
1year
Asciminib Enhances Its Treatment Efficacy Synergistically in the Treatment of Chronic Myeloid Leukemia Harboring ABL1 Kinase Domain Mutation When Combined with a Reduced Dose of Ponatinib, Dasatinib, or Bosutinib, but Not with Nilotinib or Imatinib (ASH 2023)
The present study demonstrated that a half of baseline conc ABPIs in combination with ASC is as effective as other ABPIs not just in WT but also in other ABL1 KDM CML cell lines. Different CML cell lines harboring different ABL KDM has different treatment spectrum on optimal ABPI drug as well as optimal drug conc. This result will be useful to design future clinical trial of dual blockade of ASC with other ABPIs considering the ABL KDM profiles.
Clinical
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 E255K • BCR-ABL1 F317L • BCR-ABL1 G250E • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 M351T • BCR-ABL1 H396P • BCR-ABL1 Y253F • BCR-ABL1 F317V • ABL1 E255K • BCR-ABL1 T315A • ABL1 F317L • ABL1 G250E • ABL1 M351T
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dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
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
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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)
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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
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dasatinib • Jakafi (ruxolitinib) • dexamethasone
2years
In Vitro Evidence of Double Blockade of Asciminib with Reduced Dose of ATP-Binding Pocket Inhibitors in the Treatment of Chronic Myeloid Leukemia Harboring ABL1 Kinase Domain Mutation (ASH 2022)
ASCEMBL trial showed superior efficacy of ASC to Bosutinib (BOS) with a higher molecular response rate, and a lower rate of discontinuation due to lack of efficacy (24.2% vs 35.5% at week 96)...A phase 1 study attempted to determine appropriate dose of ASC in combination with fixed dose of ABPIs including Imatinib (IMA), Dasatinib (DAS) and Nilotinib (NIL)...Each cell lines does have its inherent resistance level to double blockades, which needs to be further explored. A phase 1 study with reduced dose of ABPI in combination with fixed dose ASC is strongly warranted to define an optimal dose for combination.
Preclinical
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 E255K • BCR-ABL1 Y253H • BCR-ABL1 G250E • BCR-ABL1 M244V • BCR-ABL1 M351T • BCR-ABL1 Y253F • BCR-ABL1 F317V • ABL1 E255K • ABL1 G250E • ABL1 M351T • ABL1 Y253H
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dasatinib • imatinib • Tasigna (nilotinib) • 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
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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)
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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
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dasatinib • Jakafi (ruxolitinib) • dexamethasone
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
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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)
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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
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dasatinib • Jakafi (ruxolitinib) • dexamethasone