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BCR (BCR Activator Of RhoGEF And GTPase)
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4d
Successful treatment with venetoclax and azacitidine in a patient with acute myeloid leukemia with BCR::ABL1 fusion (PubMed, Rinsho Ketsueki)
A bone marrow examination after two cycles confirmed the maintenance of hematological remission, and RT-PCR showed reduced minor BCR-ABL mRNA levels. AML with BCR-ABL1 fusion generally has a poor prognosis and has no established treatment, but in this case, treatment with venetoclax and azacitidine successfully induced remission and demonstrated potential efficacy against BCR-ABL fusion-positive clones.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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BCR-ABL1 fusion • ABL1 fusion
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Venclexta (venetoclax) • azacitidine
5d
CARPALL: Immunotherapy with CD19+CD22 CAR T-cells for CD19+ and CD22+ Acute Lymphoblastic Leukaemia (clinicaltrials.gov)
P1, N=50, Recruiting, University College, London | Active, not recruiting --> Recruiting | N=38 --> 50 | Trial completion date: Dec 2036 --> Dec 2041 | Trial primary completion date: Dec 2028 --> Dec 2026
Enrollment open • Enrollment change • Trial completion date • Trial primary completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A) • CD22 (CD22 Molecule) • TCF3 (Transcription Factor 3)
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KMT2A rearrangement
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cyclophosphamide • fludarabine IV • AUTO1/22
7d
EDI-PIO: Study of Imatinib Discontinuation in Chronic Myeloid Leukemia with Deep Molecular Response (clinicaltrials.gov)
P2, N=31, Completed, University of Campinas, Brazil | Active, not recruiting --> Completed
Trial completion
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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imatinib
7d
UKALL14: Standard Chemotherapy with or Without Nelarabine or Rituximab in Treating Patients with Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov)
P=N/A, N=0, Completed, University College, London | Active, not recruiting --> Completed | N=1033 --> 0 | Trial completion date: Dec 2025 --> Feb 2025
Trial completion • Enrollment change • Trial completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
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Rituxan (rituximab) • imatinib • cytarabine • cyclophosphamide • etoposide IV • vincristine • daunorubicin • melphalan • Oncaspar liquid (pegaspargase) • fludarabine IV • nelarabine • mercaptopurine • Kepivance (palifermin)
9d
Resveratrol-Induced Modulation of Key Genes and DNA Fragmentation in Chronic Myeloid Leukemia Cells. (PubMed, Asian Pac J Cancer Prev)
These findings suggest that resveratrol exerts anti-proliferative and pro-apoptotic effects in CML cells by modulating key genes and induction of DNA fragmentation, highlighting its potential as a therapeutic agent for CML treatment.
Journal • IO biomarker
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • VDAC1 (Voltage Dependent Anion Channel 1)
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BCR-ABL1 fusion
10d
Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop) (clinicaltrials.gov)
P2, N=163, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
Trial completion
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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Tasigna (nilotinib)
10d
Bone Marrow CD34+/lin- Cells of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) After 12 Months of Nilotinib Treatment Exhibit a Different Gene Expression Signature Compared to the Diagnosis and the Corresponding Cells from Healthy Subjects. (PubMed, Cancers (Basel))
We observed that certain transcriptome features present at diagnosis persisted after 12 months of nilotinib treatment, compared to CTRLs. This suggests that nilotinib may exert selective pressure, potentially supporting the survival and self-renewal of LSCs. Future insights into these pathways could help identify therapeutic targets to improve outcomes in CML.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD34 (CD34 molecule)
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BCR-ABL1 fusion
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Tasigna (nilotinib)
10d
SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression. (PubMed, Oncogene)
Furthermore, targeting SUMOylation of BCR-ABL restrained the proliferation of TKI-resistant CML cells. These results identify the mechanism by which TRIM28 maintains BCR-ABL stability to promote CML progression and suggest SUMOylation as a target for CML treatment.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • TRIM28 (Tripartite Motif Containing 28)
11d
Periorbital edema and phototoxic rash associated with dasatinib: A case report. (PubMed, SAGE Open Med Case Rep)
In this case, a phototoxic rash that developed in a 78-year-old bcr-abl positive acute lymphoblastic leukemia patient is presented. This case supports that phototoxic reactions may occur with dasatinib and emphasizes that clinicians should be alert for this side effect.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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dasatinib
11d
Cardiac arrhythmias of BCR-ABL inhibitors with or without triazole antifungal agents: A real-world pharmacovigilance study based on the food and drug administration adverse event reporting system database. (PubMed, SAGE Open Med)
The reporting odds ratios and their 95% confidence intervals for BCR-ABL inhibitor monotherapy, asciminib, nilotinib, and ponatinib were 1.31 (1.27-1.36), 2.11 (1.45-3.06), 2.66 (2.53-2.80), and 1.18 (1.05-1.33), respectively. Dasatinib plus triazole antifungal agents (reporting odds ratio: 2.98, 95% CI: 1.93-4.60) and ponatinib plus triazole antifungal agents (reporting odds ratio: 1.53, 95% CI: 1.08-2.16) were associated with a higher disproportionality of cardiac arrhythmias than BCR-ABL inhibitor monotherapy. The median time-to-onset was longer with monotherapy than with BCR-ABL inhibitors plus triazole antifungal agents (2.63 vs. 0.34 months, p < 0.001), both indicating an early failure type. BCR-ABL inhibitors plus triazole antifungal agents increase the risk of cardiac arrhythmia, particularly in the early stages of treatment, with the risk decreasing over time.
Journal • Adverse events • Real-world evidence
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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dasatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Scemblix (asciminib)
13d
Imatinib Mesylate or Dasatinib in Treating Patients With Previously Untreated Chronic Phase Chronic Myelogenous Leukemia (clinicaltrials.gov)
P2, N=406, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2025 --> Mar 2026
Trial completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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dasatinib • imatinib
13d
ABL001 for the Treatment of Chronic Myeloid Leukemia in Patients Who Are on Therapy With Tyrosine Kinase Inhibitor (clinicaltrials.gov)
P2, N=7, Terminated, M.D. Anderson Cancer Center | N=40 --> 7 | Trial completion date: Dec 2025 --> Mar 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Mar 2025; 75% < Participants, Administrativley Complete
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Minimal residual disease
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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Scemblix (asciminib)
17d
Characteristics and outcome of pediatric mixed-phenotype acute leukemia treated with EORTC 58951 protocol: An observational study in Tunisia. (PubMed, Arch Pediatr)
MPAL is rare and complex, with heterogeneous clinical and biological features. A literature review suggests that ALL chemotherapy is better for achieving a favorable prognosis than AML regimens.
Observational data • Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A)
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KMT2A rearrangement
18d
Decitabine, Venetoclax, and Ponatinib for the Treatment of Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase or Accelerated Phase Chronic Myelogenous Leukemia (clinicaltrials.gov)
P2, N=30, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
Enrollment open • IO biomarker
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2)
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Venclexta (venetoclax) • Iclusig (ponatinib) • decitabine
18d
Decitabine in Treating Patients With Myelofibrosis (clinicaltrials.gov)
P2, N=21, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2025 --> Feb 2026
Trial completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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decitabine
18d
Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia (clinicaltrials.gov)
P2, N=156, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025
Trial completion • Trial completion date • Trial primary completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IFNA1 (Interferon Alpha 1)
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dasatinib
19d
Selective translational control by PABPC1 phase separation regulates blast crisis and therapy resistance in chronic myeloid leukaemia. (PubMed, Nat Cell Biol)
Moreover, we identified two PABPC1 inhibitors that inhibited BC progression and overcame TKI resistance in murine and human CML. Overall, our work identifies PABPC1 as a selective translation enhancing factor in CML-BC, with its genetic or pharmacological inhibition overcoming TKI resistance and suppressed BC progression.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1)
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BCR-ABL1 fusion
20d
ASC4MORE: Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) (clinicaltrials.gov)
P2, N=104, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
Trial completion
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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imatinib • Tasigna (nilotinib) • Scemblix (asciminib)
21d
DESTINY: De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia (clinicaltrials.gov)
P2, N=174, Completed, University of Liverpool | Unknown status --> Completed
Trial completion
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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dasatinib • imatinib
21d
CRISPR screening reveals ZNF217 as a vulnerability in high-risk B-cell acute lymphoblastic leukemia. (PubMed, Theranostics)
Furthermore, we characterized FOS as a functionally essential downstream target of ZNF217, and ZNF217 inhibited FOS expression in a CoREST-independent manner. Our findings highlight ZNF217 as a promising therapeutic target for the treatment of high-risk B-ALL, such as those carrying MLL-rearrangements or BCR-ABL fusion.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A) • ZNF217 (Zinc Finger Protein 217)
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MLL rearrangement
21d
CD19-targeted HSP90 inhibitor nanoparticle combined with TKIs reduces tumor burden and enhances T-cell immunity in murine B-cell malignancies. (PubMed, Theranostics)
CD19@NP/17-DMAG nanoparticles demonstrated enhanced efficacy in murine models of BCR-ABL1⁺ B-cell acute lymphoblastic leukemia (B-ALL) when combined with tyrosine kinase inhibitors (TKIs), including the BCR-ABL1-targeted imatinib and the broad-spectrum ponatinib. In addition, CD19@NP/17-DMAG was effective in another B-cell malignancy model, A20 lymphoma, significantly slowing tumor growth and amplifying T-cell responses. These findings highlight the CD19@NP/17-DMAG system as a promising therapeutic approach that both augments T cell immune responses and minimizes side effects in B-cell malignancies.
Preclinical • Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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imatinib • Iclusig (ponatinib)
22d
Asciminib: the tyrosine kinase inhibitor with a unique mechanism of action. (PubMed, Expert Opin Pharmacother)
Imatinib (first generation), dasatinib, nilotinib and bosutinib (second generation) and ponatinib (third generation) are the five approved TKIs that inhibit BCR::ABL1 by binding to the ATP binding site of ABL1. In this review we detail the mechanism of action, preclinical data, clinical data, safety and tolerability of asciminib. Due to its mechanism of action, asciminib has fewer off target effects, resulting in an improved safety and tolerability profile.
Review • Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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ABL1 T315I
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dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
24d
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2)
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Jakafi (ruxolitinib)
24d
SMYD3 Activates Fatty Acid β-oxidation to Promote Self-Renewal of Leukemia Stem Cells. (PubMed, Cancer Res)
Blocking CPT1A-mediated FAO reduced the function of human CML LSCs in vitro and depleted LSCs in vivo. These findings shed light on the role of histone lysine methylation-mediated FAO in the maintenance of LSCs and suggest that SMYD3 may serve as a therapeutic target for treating patients with CML.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD34 (CD34 molecule) • SMYD3 (SET And MYND Domain Containing 3) • CPT1A (Carnitine Palmitoyltransferase 1A) • FABP5 (Fatty Acid Binding Protein 5)
25d
Discovery of N-(2-Acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide Derivatives as Novel Potential BCR-ABL1 Inhibitors Through Structure-Based Virtual Screening. (PubMed, Molecules)
The most potent compound, 10m, demonstrated inhibition of BCR-ABL-dependent signaling and showed an anti-tumor effect against K562 cells, with an IC50 value of 0.98 μM. Compound 10m displayed powerful synergistic anti-proliferation and pro-apoptotic effects when combined with asciminib, highlighting its potential as a promising lead for the development of potential BCR-ABL inhibitors.
Journal
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BCR (BCR Activator Of RhoGEF And GTPase)
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Scemblix (asciminib)
25d
ENESTFreedom: Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients (clinicaltrials.gov)
P2, N=215, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
Trial completion • Minimal residual disease
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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Tasigna (nilotinib)
1m
Study of Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia With Inotuzumab Ozogamicin (InO) (clinicaltrials.gov)
P2, N=25, Recruiting, University of Chicago | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Mar 2025 --> Mar 2027
Trial completion date • Trial primary completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD22 (CD22 Molecule)
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dasatinib • Iclusig (ponatinib) • Besponsa (inotuzumab ozogamicin) • vincristine
1m
ASC4TARGET: Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib. (clinicaltrials.gov)
P2, N=20, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
Enrollment open
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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Iclusig (ponatinib) • Scemblix (asciminib)
1m
Allelic expression imbalance of CDKN2A variants in childhood acute lymphoblastic leukemia. (PubMed, Cell Oncol (Dordr))
These findings illuminate how inherited CDKN2A genetic variations of coding region influence ALL development through AEI mechanisms.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CRLF2 (Cytokine Receptor Like Factor 2)
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NRAS G12
1m
HQP1351CC203: A Pivotal Study of HQP1351 in Patients With Chronic Myeloid Leukemia in Chronic Phase (clinicaltrials.gov)
P2, N=144, Completed, Ascentage Pharma Group Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2024 | Trial primary completion date: Dec 2024 --> Aug 2024
Trial completion • 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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dasatinib • imatinib • Tasigna (nilotinib) • Nailike (olverembatinib) • Synribo (omacetaxine mepesuccinate) • hydroxyurea
1m
ASC4KIDS: Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia (clinicaltrials.gov)
P1/2, N=34, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jun 2026 --> Jul 2025
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)
1m
Clinical characteristics and prognosis of ALL in children with CDKN2A/B gene deletion. (PubMed, Exp Biol Med (Maywood))
These results suggest that CDKN2A/B deletion may be one of the factors affecting poor prognosis. It provides a new perspective for clinical treatment, risk stratification, and prognostic assessment in pediatric ALL patients.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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CDKN2A deletion
1m
ASC4OPT: Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. (clinicaltrials.gov)
P3, N=169, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Apr 2026 --> Mar 2024
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)
1m
Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)
P1, N=100, Recruiting, Jacqueline Garcia, MD | Trial primary completion date: Feb 2025 --> Dec 2025
Trial primary completion date
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)
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Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan
1m
Nilotinib attenuates vascular pathology in experimental cerebral malaria. (PubMed, Blood Adv)
Bosutinib attenuated both thrombin and parasite-induced barrier alterations, while nilotinib was only effective against thrombin, and imatinib protected against neither. Our findings provide important mechanistic insight into the activities of BCR-ABL drugs to suppress endothelial barrier disruptive signaling in vitro and protect in a mouse model of CM. These findings can inform the repurposing of these drugs in malaria treatment, particularly for managing cerebral complications.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDH5 (Cadherin 5)
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imatinib • Tasigna (nilotinib) • Bosulif (bosutinib)
2ms
Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors (clinicaltrials.gov)
P2, N=24, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=41 --> 24 | Trial completion date: Dec 2026 --> Feb 2026 | Trial primary completion date: Feb 2026 --> Feb 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
Jakafi (ruxolitinib)
2ms
Venetoclax Basket Trial for High Risk Hematologic Malignancies (clinicaltrials.gov)
P1, N=92, Recruiting, Andrew E. Place, MD | Trial completion date: Apr 2027 --> Jul 2028 | Trial primary completion date: Apr 2025 --> Jul 2026
Trial completion date • Trial primary completion date • Pan tumor
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FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1)
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KMT2A rearrangement • ABL1 fusion
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Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • azacitidine • vincristine • leucovorin calcium • Asparlas (calaspargase pegol-mknl) • dexrazoxane
2ms
CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells. (PubMed, Cell Death Discov)
Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (BCR-ABLi) are the mainstay of chronic myelogenous leukemia (CML) treatment...Dissecting the effects of pharmacological CDK8/19 inhibition on CML survival in response to BCR-ABLi, we found that a selective, non-toxic CDK8/19 inhibitor (CDK8/19i) Senexin B (SenB) and other CDK8/19i sensitized K562 cells to different BCR-ABLi via attenuation of cell cycle arrest...In contrast, IM-treated BCR-ABL-positive KU812 CML cells, which did not induce p27Kip1, readily died regardless of SenB treatment. Thus, CDK8/19i prevent the quiescence-mediated escape from BCR-ABLi-induced apoptosis, suggesting a strategy for avoiding the CML relapse.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CASP9 (Caspase 9) • ANXA5 (Annexin A5)
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imatinib • Senexin B
2ms
A041703: Inotuzumab Ozogamicin and Blinatumomab in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia (clinicaltrials.gov)
P2, N=64, Recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
Trial completion date • Trial primary completion date
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD22 (CD22 Molecule)
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CD22 positive
|
Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin)
2ms
Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors (clinicaltrials.gov)
P2, N=84, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
Trial completion
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
Scemblix (asciminib)
2ms
T cell receptors specific for an imatinib-induced mutation in BCR-ABL for adoptive T cell therapy. (PubMed, Front Immunol)
Importantly, we demonstrated that the ABL-E255V neoepitope was naturally processed and presented. In summary, our results demonstrate that HLA-A2+ CML cells harboring the E255V mutation can be targeted by specific TCRs, which may benefit patients who are highly resistant to available TKIs due to compound mutations.
Journal • IO biomarker
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD8 (cluster of differentiation 8)
|
BCR-ABL1 E255V
|
imatinib
2ms
Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia (clinicaltrials.gov)
P2, N=97, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jan 2026
Trial completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD22 (CD22 Molecule) • CD5 (CD5 Molecule) • CD79A (CD79a Molecule) • MME (Membrane Metalloendopeptidase) • CD7 (CD7 Molecule) • ANPEP (Alanyl Aminopeptidase, Membrane) • MPO (Myeloperoxidase)
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dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • sirolimus • leucovorin calcium • Hemady (dexamethasone tablets) • Neupogen (filgrastim) • Starasid (cytarabine ocfosfate)
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