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    GENE:

    BCR (BCR Activator Of RhoGEF And GTPase)

    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
    3d
    Enhanced induction of apoptosis in chronic myeloid leukemia cells through synergistic effect of telomerase inhibitor MST-312 and imatinib. (PubMed, Mol Biol Rep)
    The combination of MST-312 and imatinib shows potential as a CML therapy. However, further research and clinical trials are necessary to validate these findings and determine their clinical relevance.
    Journal • IO biomarker
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5)
    |
    BCL2 expression • MYC expression • TP53 expression • BAX expression
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    imatinib
    6d
    Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context. (PubMed, Neoplasia)
    We validated tumor suppressive activities of the AURKB inhibitor (AURKBi) Barasertib (AZD1152-HQPA) and the structurally unrelated compound GSK-1070916 in cerebellum slice culture models for SHH, and Grp3 MB...We revealed that the combination of AURKBi with the SRC/BCR-ABL inhibitor Dasatinib acts synergistically to repress tumor growth and expansion in the highly invasive MB cell model ONS-76, but not in Grp3 MB cells...In conclusion, we demonstrate that AURKB is essential for MB tumor growth and expansion in the tissue context and the inhibition of AURKB is equally efficient as irradiation in repressing tumor cell growth. In patients younger than three years, pharmacological targeting of AURKB may thus constitute a novel means to overcome radiotherapy limitations.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • AURKB (Aurora Kinase B)
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    dasatinib • barasertib-HQPA (AZD2811) • NMI-900
    6d
    Targeting DDX3X eliminates leukemia stem cells in chronic myeloid leukemia by blocking NT5DC2 mRNA translation. (PubMed, Oncogene)
    Collectively, our findings provide new evidence for RNA helicase facilitating the translation of specific mRNA in LSCs. Targeting DDX3X may represent a promising therapeutic strategy for eradication of LSCs in CML patients.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD34 (CD34 molecule) • DDX3X (DEAD-Box Helicase 3 X-Linked)
    6d
    An Overview of Myeloid Blast-Phase Chronic Myeloid Leukemia. (PubMed, Cancers (Basel))
    In order to improve treatment responses in these patients, more emphasis should be placed on understanding the biology of myeloid blastic transformation in CML and mechanisms of resistance to TKIs. Although patient numbers are small, randomized clinical trials should be considered.
    Clinical • Review • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    8d
    AALL1131: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (clinicaltrials.gov)
    P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025
    Trial completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
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    MLL rearrangement • MLL rearrangement
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    dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    8d
    Individualized Quality Control Plan (IQCP) Assessment of BCR-ABL1 p210 Transcript Quantification by GeneXpert (AMP 2024)
    Using an IQCP approach, our lab has established a quality control plan that uses weekly QC with the Xpert BCR-ABL assay. Regular review of this weekly QC data shows that this assay continues to perform well with minimal deviations in QC results during our first 18 months of patient testing.
    Clinical
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Xpert® BCR-ABL Ultra
    8d
    Development of a Synthetic Secondary Standard for the Quantification of p210 BCR-ABL1 Standardized to the International Scale (IS) (AMP 2024)
    A linear relationship was found between reported and assigned values for all levels of the reference standards when tested across 3 different BCR-ABL RT-qPCR assays, enabling the calculation of an assay-specific CF to allow harmonized reporting on the International Scale (%IS). The BCR-ABL p210 Panel was validated for accuracy, precision, robustness, and traceability, and can be used as a WHO traceable reference standard to create assay-specific CF to enable standardized reporting on the International Scale (%IS).
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    BCR-ABL1 mutation
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    ipsogen BCR-ABL1 mbcr Kit
    8d
    Capturing Fusion in Hematological Malignancies through Targeted RNASeq (AMP 2024)
    We have demonstrated the capability of the SureSeq Myeloid Fusion Complete NGS Workflow Solution to detect known rearrangements in AML. We observed 100% concordance with qPCR and FISH for all samples tested. The NGS data permitted single-exon resolution of breakpoints and revealed the presence of multiple breakpoints which would have remained undetected with FISH.
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • AFF1 (AF4/FMR2 Family Member 1) • PML (Promyelocytic Leukemia) • MECOM (MDS1 And EVI1 Complex Locus) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
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    BCR-ABL1 fusion • MLL fusion
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    SureSeq™ Myeloid Fusion Panel
    8d
    Assessing the Validity of the Cepheid Xpert BCR-ABL (p190) Real-Time RT-PCR Assay (AMP 2024)
    The validation demonstrated the Xpert P190 BCR-ABL Real-Time RT-PCR assay was very accurate and precise. The assay will be used to confirm p190 BCR::ABL transcripts in whole-blood samples and to quantitate the levels in patients undergoing treatment.
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Xpert® BCR-ABL Ultra
    8d
    Validation of the Cepheid Xpert BCR-ABL Ultra p210 and p190 Assays in Peripheral Blood and Bone Marrow Specimens (AMP 2024)
    Excellent concordance was seen between the Xpert BCRABL Ultra p210 and p190 assays compared to our institutional RT-qPCR assay in PB/BM samples. The Xpert BCR-ABL Ultra p190 and p210 assays showed distinct benefits, including near full automation, quick setup time without laborious RNA extraction, and fast turnaround time. These advancements allow us to assess PB/BM samples for p190 and p210 transcripts with high sensitivity and specificity for diagnostic and therapeutic monitoring purposes.
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    ABL1 fusion
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    Xpert® BCR-ABL Ultra
    9d
    RWE,NIS,Prospective Study for the Effectiveness, Tolerability and Adherence of Asciminib in Saudi Arabia. (ASC4REAL) (clinicaltrials.gov)
    P=N/A, N=40, Not yet recruiting, Novartis Pharmaceuticals
    New trial
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Scemblix (asciminib)
    14d
    MCC-20963: Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL) (clinicaltrials.gov)
    P2, N=25, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting
    Enrollment closed
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Inrebic (fedratinib)
    14d
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
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    MI Tumor Seek™
    14d
    5-Azacitidine and Decitabine Epigenetic Therapy for Myeloid Malignancies (clinicaltrials.gov)
    P1, N=20, Recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD14 (CD14 Molecule) • DCK (Deoxycytidine Kinase 2) • DNMT1 (DNA methyltransferase 1) • ITGAM (Integrin, alpha M) • NT5C (5', 3'-Nucleotidase, Cytosolic)
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    Chr del(5q)
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    azacitidine • decitabine
    15d
    Impact of TP53 Mutation on Survival Outcomes in Acute Lymphoblastic Leukemia at a Tertiary Center (ASH 2024)
    Because of the above, further research is needed to explore whether using upfront immunotherapy like inotuzumab ozogamicin or blinatumomab in the upfront setting, as well as administering allogeneic transplant early in the treatment course of muTP53-ALL would decrease the risk of relapse and improve long-term survival. The muTP53-ALL patients had similar CCR to first-line therapy to wtTP53-ALL. However, they had worse OS, likely because of relapses. The findings highlight the significant impact of TP53 mutation on outcomes in ALL.
    IO biomarker
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    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    TP53 mutation • TP53 wild-type • BCR-ABL1 mutation
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    clonoSEQ
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    Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin)
    15d
    Improved Outcomes of Adult Patients with Philadelphia-like Acute Lymphoblastic Leukemia (Ph-Like ALL) Treated within an Integrated Leukemia/Transplant Program with Incorporation of Pediatric Inspired Regimens and Early Allogeneic Transplant (ASH 2024)
    Blinatumomab was not used during consolidation therapy in the reported patients. Its incorporation in the routine therapy of newly diagnosed patients may increase the proportion of patients receiving AHCT in a MRD negative state and further improve outcomes in this historically poor risk patient population.
    Clinical
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • CSF1R (Colony stimulating factor 1 receptor)
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    CRLF2 rearrangement • JAK2 rearrangement
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    clonoSEQ
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    Blincyto (blinatumomab)
    15d
    Measurable Residual Disease in Adult B Lymphoblastic Leukemia: A Study of Concordance between Multiparametric Flow Cytometry, Next-Generation Sequencing of Immunoglobulin Gene Rearrangements, and Quantitative PCR (ASH 2024)
    This study involved adult patients aged 19 or older with B-ALL, treated with modified hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and allogeneic hematopoietic stem cell transplant (allogeneic-HSCT) at Catholic Hematology Hospital from May 2022 to June 2024...Poor MRD response was defined as > 0.1%, and complete MRD response as < 0.001%, and poor MRD responders were treated with MRD-directed therapy using blinatumomab or next-generation tyrosine kinase inhibitors... Our data suggested all MRD detection methods showed acceptable power and good concordance rates, but the detection power was different between Ph-positive and Ph-negative ALL. We also suggested MRD-directed therapeutic strategies might predict the significant time point of MRD for the prediction of survival outcomes.
    Clinical • Next-generation sequencing • Discordant
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD73 (5'-Nucleotidase Ecto) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD22 (CD22 Molecule) • CEACAM6 (CEA Cell Adhesion Molecule 6) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • NRP1 (Neuropilin 1)
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    LymphoTrack® Dx IGH Assay
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    doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • vincristine
    17d
    Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors (clinicaltrials.gov)
    P2, N=41, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> Dec 2026 | Trial primary completion date: Jan 2025 --> Dec 2025
    Trial completion date • Trial primary completion date • Combination therapy
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Jakafi (ruxolitinib)
    17d
    Impact of Simultaneous Presence of Multiple PML-RARA Isoforms on Phenotype in Patients with Acute Promyelocytic Leukaemia. (PubMed, J Coll Physicians Surg Pak)
    Identifying PML-RARA isoform subtypes is important for predicting prognosis and informing clinical follow-up.
    Journal
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    BCR (BCR Activator Of RhoGEF And GTPase) • PML (Promyelocytic Leukemia)
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    PML-RARA fusion
    18d
    Sex-dependent differences in hematopoietic stem cell aging and leukemogenic potential. (PubMed, Oncogene)
    Our results showed for the first time that sex-differentiated HSC aging impacts hematopoiesis, leukemogenesis, and certain gene functions. This discovery provides insights into understanding age-dependent hematological diseases and sex-targeted strategies for the treatment and prevention of certain blood disorders and cancer.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    21d
    Halving Time of BCR-ABL Transcripts as a Precise Predictor for Deep Molecular Response in Patients with Chronic Myeloid Leukemia Treated with TKI (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    In addition to BCR-ABLIS level, HT of BCR-ABLIS can be used as another important predictor of treatment efficacy in CML patients. The combination of BCR-ABLIS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.
    Retrospective data • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    imatinib
    21d
    Fluorescence Quantitative PCR Detection of ABL1 Kinase Region Mutations (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    Compared with Sanger sequencing, fluorescence quantitative PCR has higher sensitivity and can screen for low-frequency ABL1 kinase mutations in the early stage. Moreover, it can also perform relative quantitative analysis, so the method has good clinical application prospects for detecting ABL1 mutation.
    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 Y253H • ABL1 T315I • ABL1 E255K • BCR-ABL1 T315A • ABL1 Y253H • BCR-ABL1 Y253H + BCR-ABL1 T315I
    22d
    Digital Ischemia and Gangrene: An Unusual Presentation of Chronic Myeloid Leukemia. (PubMed, Cureus)
    He was found to be positive for BCR-ABL by reverse transcription polymerase chain reaction (RT-PCR), thus confirming the diagnosis of CML. He received imatinib 400 mg/day and subsequently experienced resolution of symptoms and complete hematological response by the 12th week of therapy.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    imatinib
    23d
    A Retrospective Analysis of BCR-ABL-1 Kinase Domain Mutations in Frontline TKI Resistant Chronic Myeloid Leukemia Patients: A Single Centre Experience. (PubMed, Indian J Hematol Blood Transfus)
    Patients may have have underlying TKD mutations at prestation or may develop during course of disease. In case of TKI resistance, testing for specific mutations must be done and appropriate TKI sensitive to underlying mutation is to be used which translates into improved OS.
    Retrospective data • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    23d
    Prognostic Significance of Regulatory T-Cells and PD-1 + CD8 T-Cells in Chronic Myeloid Leukemia Patients Treated with Generic Imatinib. (PubMed, Indian J Hematol Blood Transfus)
    Our findings reveal a significantly higher proportion of Tregs and PD-1 + CD8 T-cells in patients with CML-CP compared to healthy controls, notably diminished following imatinib treatment. These observations suggest the potential for immunotherapy as a promising approach to managing immune exhaustion in CML patients.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1)
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    imatinib
    23d
    Real World Outcomes with Treatment Free Remission in Chronic Myeloid Leukemia-Experience from a Tertiary Care Cancer Centre. (PubMed, Indian J Hematol Blood Transfus)
    Thirty five (92%) patients were treated with imatinib at diagnosis...On multivariate analysis, none of these factors were found to be significant. This retrospective study suggests that for CML CP patients achieving deep molecular response, discontinuing TKI therapy in real-world settings may be feasible while potentially achieving comparable outcomes.
    Journal • Real-world evidence • Real-world
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    imatinib
    23d
    ASC4OPT: Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. (clinicaltrials.gov)
    P3, N=199, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jun 2024 --> Apr 2026
    Trial primary completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Scemblix (asciminib)
    24d
    ASC2ESCALATE: Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (clinicaltrials.gov)
    P2, N=196, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Jan 2027 --> Oct 2027 | Trial primary completion date: Jan 2026 --> Sep 2025
    Enrollment closed • Trial completion date • Trial primary completion date
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    BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Scemblix (asciminib)
    24d
    Combined targeting of GPX4 and BCR-ABL tyrosine kinase selectively compromises BCR-ABL+ leukemia stem cells. (PubMed, Mol Cancer)
    In summary, the dual inhibition of GPX4 and BCR-ABL presents a promising therapeutic strategy to synergistically target blast cells and drug-insensitive LSCs in patients, offering potential avenues for advancing leukemia treatment.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • GPX4 (Glutathione Peroxidase 4) • HSPA8 (Heat Shock Protein Family A (Hsp70) Member 8)
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    GPX4 expression
    24d
    A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs (clinicaltrials.gov)
    P3, N=173, Recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: Apr 2025 --> Dec 2027 | Trial primary completion date: Jan 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    BCR-ABL1 mutation
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    imatinib • Supect (radotinib)
    26d
    Ponatinib: A Review of the History of Medicinal Chemistry behind Its Development. (PubMed, Pharmaceuticals (Basel))
    The primary treatment for chronic myeloid leukemia (CML) involves first- and second-generation tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, bosutinib, and dasatinib. It includes in silico calculations, such as the octanol/water partition coefficient (cLogP) via SwissAdme, and 2D maps of intermolecular interactions through molecular docking. This approach enhances understanding for both specialists and those interested in medicinal chemistry and pharmacology, while also contextualizing future directions for further optimizations of ponatinib, facilitating the development of new analogs of this crucial inhibitor for the treatment of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
    Review • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    BCR-ABL1 T315I • ABL1 T315I • BCR-ABL1 mutation
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib)
    28d
    Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL (clinicaltrials.gov)
    P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2024 --> Apr 2025
    Trial completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    everolimus • Kisqali (ribociclib) • dexamethasone
    29d
    Correlation of T Regulatory Cells, Cytotoxic T-lymphocyte-associated Antigen 4, and Transforming Growth Factor-β1 with Treatment Response in Patients with Chronic Myeloid Leukemia Receiving Dasatinib Therapy. (PubMed, Ann Afr Med)
    The study concluded that dasatinib treatment improved response in CML patients with decreased Treg cells. Dasatinib reduces Treg-mediated immunological suppression, reducing CTLA-4 and TGF-β1 levels.
    Journal
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    BCR (BCR Activator Of RhoGEF And GTPase) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TGFB1 (Transforming Growth Factor Beta 1)
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    dasatinib • imatinib
    30d
    Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia. (PubMed, Cancer Res)
    In this study, we developed a potent SOS1 PROTAC SIAIS562055, which was designed by connecting a CRBN ligand to an analogue of the SOS1 inhibitor BI-3406...SIAIS562055 and BCR-ABL inhibitors synergistically enhanced inhibition of ABL phosphorylation and downstream signaling, demonstrating robust antitumor activities in both mouse xenografts and primary CML patient samples. In summary, this study suggests that PROTAC-mediated SOS1 degradation represents an effective therapeutic strategy for treating not only KRAS-mutant cancers but also BCR-ABL-harboring leukemia.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CRBN (Cereblon)
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    KRAS mutation
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    BI-3406
    1m
    A Study to Investigate the Safety and Efficacy of KQB198 As Monotherapy and in Combination in Participants with Advanced Hematologic Malignancies (clinicaltrials.gov)
    P1, N=122, Recruiting, Kumquat Biosciences Inc.
    New P1 trial • Combination therapy • Metastases
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    dasatinib
    1m
    Non-fused Pyrimidine Derivatives as Potential Pharmacological Entities: A Review. (PubMed, Curr Top Med Chem)
    The review details the importance of morpholine, piperidine, and pyrrolidine ring substitutions on pyrimidine moiety as well as the role of H-bonding and amino linkage along with antibacterial activity due to the presence of pleuromutilin and tetrazole molecules. Researchers were motivated to develop and enhance the non-fused pyrimidine scaffold to uncover novel medicines by reading this review article.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDK2 (Cyclin-dependent kinase 2) • EPHB4 (EPH receptor B4)
    1m
    BETULINIC ACID ACTS IN SYNERGISM WITH IMATINIB MESYLATE TRIGGERING APOPTOSIS IN MDR LEUKEMIA CELLS. (PubMed, Planta Med)
    Analysis of annexin V labelling demonstrated that combination of IMA with betulinic acid enhances the inhibition on cell proliferation via apoptosis pathway, with caspases 3/7 activation after 24 hours of treatment, and inhibition of the STAT5/Survivin pathway, decreasing cell viability. The combination of natural products and IMA on a multidrug-resistant leukemia cell line is a promising strategy for CML treatment.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BIRC5 (Baculoviral IAP repeat containing 5) • CASP7 (Caspase 7) • ANXA5 (Annexin A5)
    |
    imatinib
    1m
    How I Treat Older Patients with Ph/BCR-ABL-Negative Acute Lymphoblastic Leukemia. (PubMed, Blood)
    Progress has been made in tailoring moderately intensive chemotherapy protocols for Ph/BCR-ABL (Ph) negative ALL in older patients, and recent phase II studies have explored integrating immunotherapy into initial treatment with very promising results. However, establishing new standard regimens for this age group remains and improving general management strategy is a pending task.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    1m
    Study of TRAIL and SAHA Co-Treatment on Leukemia K562 Cell Line. (PubMed, Cell Biochem Biophys)
    Furthermore, it was shown that DR4, DR5, and CHOP expressions were enhanced, and PI3K, Akt, ERK, STAT3, c-FLIPL, NF-κB, and BCR-ABL expressions were decreased by SAHA in K562 cells. Our study indicated that SAHA combined with TRAIL can increase the sensitivity of K562 leukemic cells to TRAIL by suppressing intracellular anti-apoptotic molecules and augmenting the expressions of DR4/DR5 and CHOP.
    Preclinical • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • STAT3 (Signal Transducer And Activator Of Transcription 3) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • CFLAR (CASP8 and FADD-like apoptosis regulator) • ANXA5 (Annexin A5) • PI3K (Phosphoinositide 3-kinases)
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    Zolinza (vorinostat)
    1m
    Insights into existing and futuristic treatment approach for chronic myeloid leukaemia. (PubMed, Indian J Med Res)
    This review provides insights into existing CML diagnoses, treatment modalities, resistance mechanisms, drugs under trial phases and new potential therapeutic drugs. Furthermore, the review looks ahead to a visionary perspective wherein the CRISPR/Cas9 approach holds the potential to evolve into a prospective curative measure for CML.
    Review • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    BCR-ABL1 fusion
    1m
    Pharmacological effects of small molecule BCR-ABL tyrosine kinase inhibitors on platelet function. (PubMed, J Pharmacol Exp Ther)
    As tyrosine kinases serve pivotal roles in platelet hemostatic function, we investigated the potential impact of both established and emerging ABL TKIs on human platelet activities ex vivo Our study included standard-of-care agents (e.g., imatinib and nilotinib), and second-generation ABL inhibitors including ponatinib and bosutinib designed to mitigate drug resistance. Significance Statement This study examines the effects of clinically relevant small molecule BCR-ABL tyrosine kinase inhibitors (TKIs) on platelet activity. This analysis includes first-time assessments of agents such as asciminib and ELVN-919 on human platelet function ex vivo, alongside established therapies (e.g., imatinib, ponatinib) with well-characterized effects on platelet function, to discern potential anti-platelet and other effects of BCR-ABL TKIs and inform clinical safety.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    2ms
    Dasatinib-Induced Bilateral Chylothorax: A Case Report. (PubMed, Cureus)
    Dasatinib was discontinued and bosutinib was initiated. Six months later, the patient remained stable with no recurrence of chylothorax. The mechanism of dasatinib-induced chylothorax is currently under investigation. The purpose of this report is to raise awareness about dasatinib-induced chylothorax, aid in identifying predisposing risk factors, and enhance understanding of the proper management of this rare complication.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    dasatinib • Bosulif (bosutinib)