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BIOMARKER:

BCR-ABL1 F317L

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:
4ms
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)
5ms
Sustaining molecular response with very low dose ponatinib and further response after hemodialysis initiation in a patient with chronic myeloid leukemia (PubMed, Rinsho Ketsueki)
He was treated with imatinib, nilotinib, and dasatinib, but failed to achieve a complete cytogenetic response (CCyR). Chronic renal failure may cause hyperabsorption and metabolic retardation in patients receiving PON. Initiation of hemodialysis may improve homeostasis resulting in enhanced anti-tumor immunity against CML.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 F317L • BCR-ABL1 mutation • ABL1 F317L
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dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib)
5ms
Dasatinib and CAR-T Cell Therapy for Newly Diagnosed Ph-Positive Acute Lymphoblastic Leukemia in Adults (ASH 2023)
Dasatinib in combination with a two-week vincristine and glucocorticoids regimen were administered, followed by sequential infusions of CD19 and CD22 CAR-T cells. Conclusions Dasatinib in combination with CAR-T cell therapy has enabled chemotherapy-free treatment in newly diagnosed Ph-positive ALL. This treatment is characterized by high complete molecular response, high long-term survival, low toxicity and short treatment cycles.
Clinical • CAR T-Cell Therapy • IO biomarker
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ABL1 (ABL proto-oncogene 1) • CD22 (CD22 Molecule)
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BCR-ABL1 F317L • BCR-ABL1 Y253H • ABL1 F317L • ABL1 Y253H
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dasatinib • vincristine • CD19/CD22 CAR-T cell therapy • anti-CD22 CAR-T cell therapy
5ms
A New Next-generation sequencing based assay for BCR-ABL1 kinase domain mutation detection in patients with chronic myeloid leukemia (AMP 2023)
In summary, our newly developed assay can be used for kinase domain mutation analysis from clinical samples and with very good sensitivity of 2%, which is in a well-acceptable range of 1% to 3% and is available on commonly used the Ion Torrent platform. This ability of the assay in detecting low-level variants and even compound variants makes it very important for selection of appropriate TKIs for CML patients.
Clinical • Next-generation sequencing
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 F317L • BCR-ABL1 Y253H • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 H396R • BCR-ABL1 Y253F • BCR-ABL1 mutation • BCR-ABL1 E355G • BCR-ABL1 E459K • BCR-ABL1 L387M • ABL1 F317L • ABL1 L387M • ABL1 Y253H
8ms
Genetic alterations in the BCR-ABL1 fusion gene related to imatinib resistance in chronic myeloid leukemia. (PubMed, Leuk Res)
One patient had co-expression of e14a2 and e14a8 transcripts. The results identify candidate single nucleotide variants and co-expressed BCR-ABL1 transcripts in cellular resistance to imatinib.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 fusion • BCR-ABL1 F317L • ABL1 F317L • BCR expression • BCR-ABL1 F311I
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imatinib
8ms
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
over1year
Differences in Variants in the Structural Domain of BCR-ABL1 Kinase between Chinese Han and Minority Patients with Chronic Myeloid Leukemia by Sanger Sequencing and Next-Generation Sequencing. (PubMed, Cytogenet Genome Res)
In conclusion, there is no significant difference in BCR-ABL1 KD mutations between Han and ethnic minority patients. NGS has a higher mutation detection rate than SS, and can detect compound variants and genes with lower mutation frequency that are not detected by SS.
Journal • Next-generation sequencing
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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 Y253H • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 D276G • BCR-ABL1 F359I • BCR-ABL1 mutation • ABL1 E255K • BCR-ABL1 E459K • ABL1 D276G • ABL1 F317L • ABL1 Y253H • BCR-ABL1 F359 • BCR-ABL1 L387F
almost2years
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
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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 V299L • BCR-ABL1 F317L • BCR-ABL1 Y253H • ABL1 T315I • ABL1 E255K • ABL1 F317L • ABL1 Y253H
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Iclusig (ponatinib)
over2years
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
3years
Discovery of a highly potent kinase inhibitor capable of overcoming multiple imatinib-resistant ABL mutants for chronic myeloid leukemia (CML). (PubMed, Eur J Pharmacol)
Although dasatinib and nilotinib have been approved as second-line therapies that could overcome some of these mutants, the most prevalent gatekeeper T315I mutant remains unconquered. CHMFL-48 also exhibited great anti-leukemic efficacies in vivo in K562 cells and p210-T315I-transformed BaF3 cell-inoculated murine models. This discovery extended the pharmacological diversity of BCR-ABL kinase inhibitors and provided more potential options for anti-CML therapies.
Journal
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CRKL (CRK Like Proto-Oncogene, Adaptor Protein)
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BCR-ABL1 E255K • BCR-ABL1 F317L • BCR-ABL1 M351T • BCR-ABL1 Y253F
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dasatinib • imatinib • Tasigna (nilotinib)
over3years
Clinical • New trial
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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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
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dasatinib • imatinib • Tasigna (nilotinib) • Hansoh Xinfu (flumatinib)
over3years
[VIRTUAL] Phase 1 Trial of Vodobatinib, a Novel Oral BCR-ABL1 Tyrosine Kinase Inhibitor (TKI): Activity in CML Chronic Phase Patients Failing TKI Therapies Including Ponatinib (ASH 2020)
Vodobatinib was evaluated over 9 escalating doses. Comparable and promising efficacy was noted in both PT (50% CCyR) and PN (67% CCyR) groups, meriting further study of vodobatinib as a potential new agent for treatment of previously treated CP-CML.
Clinical • P1 data
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 F317L • BCR-ABL1 Y253H • BCR-ABL1 E255V • ABL1 T315I • ABL1 F317L • ABL1 Y253H
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Iclusig (ponatinib)
over3years
[VIRTUAL] Clonal Hematopoiesis with Somatic Mutations in „AYA“ Generation of Patients with Chronic Myeloid Leukemia (ASH 2020)
In patient #6, G645delinsGWfs was found at the diagnosis and on the 3rd line nilotinib treatment...In patient #3, the CSF3R mutation A593V was found at diagnosis and confirmed 14 months after the imatinib initiation...Despite the clonal hematopoiesis with somatic mutations is considered as age-related phenomenon, in AYA CML patients, it may represent a critical problem in achieving sustained molecular response on solo TKI therapy, or even worse, it may result in higher risk of therapy failure and disease progression. Supported by MZCR 00023736
Clinical
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ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ATRX (ATRX Chromatin Remodeler) • CSF3R (Colony Stimulating Factor 3 Receptor) • SIRT1 (Sirtuin 1)
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BCR-ABL1 T315I • ASXL1 mutation • BCR-ABL1 E255K • BCR-ABL1 F317L • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 M351T • BCR-ABL1 Q252H • BCR-ABL1 V379I • ABL1 E255K • ABL1 F317L • ABL1 M351T
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imatinib • Tasigna (nilotinib)
4years
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