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BIOMARKER:

BCR-ABL1 M244V

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:
1m
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)
2ms
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 • ABL1 E255K • BCR-ABL1 E459K • BCR-ABL1 mutation • ABL1 D276G • ABL1 F317L • ABL1 Y253H • BCR-ABL1 F359 • BCR-ABL1 L387F
7ms
MULTI-CENTER CHART REVIEW STUDY EXAMINING TREATMENT PATTERNS AND CLINICAL OUTCOMES AMONG PATIENTS WITH CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) TREATED IN THIRD-LINE (3L) OR LATER IN FRANCE (EHA 2022)
TKIs received in 3L were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). The mean number of AEs per patient was 2.7; infections (18%) and asthenia (13%) were the more commonly documented AEs. Conclusion CP-CML patients continue to experience a substantial disease burden and poor prognosis after 3L treatment with available TKIs, underscoring the need for novel therapies that are well tolerated and can achieve durable responses.
Clinical • Clinical data • Review
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 T315I • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 F359I • BCR-ABL1 mutation • BCR-ABL1 F359
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dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib)
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
1year
Custom High Throughput Drug Sensitivity Assay Reveals Therapeutic Options for Chronic Myeloid Leukemia Patients Resistant to or Intolerant of Tyrosine Kinase Inhibitors (ASH 2021)
For new diagnosis patients, the TKIs imatinib, dasatinib, nilotinib, bosutinib, and ponatinib ranked in the top 8 drugs...In 2 patients harboring NRAS mutations, IC50 for trametinib was less than 0.1 µM as compared to patients without NRAS mutations, where the IC50s were higher...Conclusion . In vitro drug sensitivity testing provides data for potential agents for patients with resistance or intolerance to FDA approved TKIs, or those that have entered accelerated phase or blast phase.
Clinical
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ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CD19 (CD19 Molecule) • TET2 (Tet Methylcytosine Dioxygenase 2) • NCAM1 (Neural cell adhesion molecule 1)
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NRAS mutation • BCR-ABL1 M244V • JAK2 V617F • ABL1 T315I • BCR-ABL1 F359I • BCR-ABL1 F359
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Mekinist (trametinib) • dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib)
almost2years
[VIRTUAL] BCR-ABL1 Kinase Domain Mutations in Front-Line Drug Intolerant or Resistant Chronic Myeloid Leukemia Patients in India: A Single Laboratory Experience (USCAP 2021)
This study shows the incidence and pattern of mutations in one of the largest sets of Indian CML patients. It has been demonstrated that T315I is the most common mutation observed in the Indian population. However the access to the only eligible TKI- Ponatinib by the economically challenged must be addressed .
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 M244V • ABL1 T315I • ABL1 E255K • BCR-ABL1 mutation
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Iclusig (ponatinib)
almost2years
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 E355G • BCR-ABL1 L387M • BCR-ABL1 mutation • ABL1 F317L • ABL1 L387M • ABL1 M351T
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dasatinib • imatinib • Tasigna (nilotinib) • Hansoh Xinfu (flumatinib)
2years
[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)
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