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BIOMARKER:

ABL1 G250E

i
Other names: ABL proto-oncogene 1, ABL, c-ABL, JTK7, p150, ABL1
Entrez ID:
Twitter
Trials
3ms
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)
3ms
The First Report of Third-Generation TKI Olverembatinib in Adult Ph/BCR-ABL1-Positive Acute Lymphoblastic Leukemia with T315I Mutation and Relapsed Disease (ASH 2022)
Methods In this exploratory study, adult Ph/BCR-ABL1+ ALL pts with T315I mutation or disease progression were treated with olverembatinib monotherapy (40 mg, every 2 days) or in combination with VP based low intensive chemotherapy (Vincristine/Prednisone) in our institution...Meanwhile, the olverembatinib-based therapy was well-tolerated, and the main adverse events of the third-generation TKIs, such as cytopenia, elevated transaminases, hypertension, and cardiovascular events, were less frequent than those reported relating to ponatinib...Conclusion This work suggests that Olverembatinib is a very promising 3rd-generation TKI. It is effective and safe in Chinese adult Ph/BCR-ABL1+ ALL with extremely poor prognosis, especially in T315I mutated or relapsed pts.
Clinical
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 Y253H • BCR-ABL1 G250E • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 mutation • ABL1 G250E • ABL1 Y253H
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Iclusig (ponatinib) • vincristine • prednisone • Nailike (olverembatinib)
1year
P-Loop mutations-Negative prognosticators in tyrosine kinase inhibitors resistant chronic myeloid leukemia patients. (PubMed, Int J Lab Hematol)
The presence of P-Loop domain mutations negatively impacted the prognosis of the disease in terms of disease advancement and overall survival. So, the timely performance of the BCR-ABL1 mutational analysis and the modifications in the treatment plan based on the mutation identified would help in a better outcome of the disease.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 Y253H • BCR-ABL1 E255V • BCR-ABL1 G250E • BCR-ABL1 Y253F • BCR-ABL1 mutation • ABL1 G250E • ABL1 Y253H
1year
Tyrosine kinase domain mutations in chronic myelogenous leukemia patients: A single center experience. (PubMed, J Postgrad Med)
Y253F mutation was not seen in the present study sample. In the present cohort of 83 patients, 29 (35%) cases were positive for single mutation, 12 (14%) had two mutations and 3 (4%) had three mutations.
Clinical • Journal
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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 G250E • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 M351T • BCR-ABL1 Y253F • ABL1 E255K • ABL1 G250E • ABL1 M351T
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imatinib
2years
[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
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ABL1 (ABL proto-oncogene 1)
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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
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imatinib • Tasigna (nilotinib) • tacrolimus XR