our Premium Content: News alerts, weekly reports and conference planners

GENE:

BCR (BCR Activator Of RhoGEF And GTPase)

News alerts, weekly reports and conference planners

A Self-Assembled Nano-Molecular Glue (Nano-mGlu) Enables GSH/H2O2-Triggered Targeted Protein Degradation in Cancer Therapy. (PubMed, J Am Chem Soc)

Subsequent in vivo antitumor studies with a K562-xenografted mouse model indicated that Cle-NP was highly effective in tumor-specific degradation of endogenous Bcr-Abl expressed in K562 cells, leading to eventual tumor regression while maintaining good biosafety profiles. With key advantages of generality in molecular glue design, targeted delivery (e.g., H1-mGlu), potent antitumor activity partially induced by target-specific degradation, and minimized collateral damage to healthy tissues, our self-assembled nano-mGlu strategy thus provides a novel approach that might hold a significant promise for effective and personalized cancer therapy.

1 day ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • FGFR (Fibroblast Growth Factor Receptor)

Cardiovascular toxicity risk assessment of tyrosine kinase inhibitors: a pharmacovigilance study using the VigiBase database. (PubMed, Front Pharmacol)

Significant cardiovascular signals were identified for 17 TKIs, including erlotinib, gefitinib, and imatinib...Heatmaps indicated significant signals for drugs such as lapatinib in males and gefitinib in younger patients...These results underscore the importance of individualized risk assessment and management of TKI-treated patients. In conclusion, this study provides valuable insights into the cardiotoxic risk of TKIs, which is essential for developing tailored treatment plans.

4 days ago

Journal • Adverse events

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

erlotinib • gefitinib • imatinib • lapatinib

The Synchronous Diagnosis of Multiple Myeloma (MM) and Chronic Myeloid Leukemia (CML). (PubMed, Cureus)

Both cancers were aggressively treated. The patient received autologous stem cell transplantation (ASCT) for multiple myeloma and tyrosine kinase inhibitor for chronic myeloid leukemia concurrently to achieve the complete response.

6 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

PRMT1 Promotes the Self-renewal of Leukemia Stem Cells by Regulating Protein Synthesis. (PubMed, Adv Sci (Weinh))

Pharmacological inhibition of PRMT1 activity by MS023 remarkably eliminates LSCs and prolongs the survival of CML mice...PRMT1 augments the global protein synthesis via RPL29 in CML LSCs. Taken together, the findings provide new evidence that histone arginine methylation modification regulates protein synthesis in LSCs and highlight PRMT1 as a valuable druggable target for patients with CML.

9 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PRMT1 (Protein Arginine Methyltransferase 1)

MS023

13d

Efficacy of Dendritic Cell Therapy for Myeloid Leukemia and Myeloma (clinicaltrials.gov)

P2, N=38, Completed, Zwi Berneman | Unknown status --> Completed

13 days ago

Trial completion

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • WT1 (WT1 Transcription Factor)

13d

Chemotherapeutic potential of radotinib against blood and solid tumors: A beacon of hope in drug repurposing. (PubMed, Bioorg Chem)

Several second-generation tyrosine kinase inhibitors (2GTKIs), such as nilotinib, dasatinib, bosutinib, and radotinib (RTB), followed the groundbreaking introduction of imatinib. This review is the first attempt that extensively presents a compilation of data on RTB and describes its therapeutic potential against blood and solid tumors. Further investigations on RTB could expand its chemotherapeutic usage in various solid tumors and enhance the possibility of drug repurposing in cancer therapy.

13 days ago

Review • Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

dasatinib • imatinib • Tasigna (nilotinib) • Bosulif (bosutinib) • Supect (radotinib)

16d

Exploring Inhibition Mechanisms in Wildtype and T315I BCR-ABL1: An In Silico Approach Integrating Virtual Screening, MD Simulations, and MM-GBSA Analysis. (PubMed, J Comput Chem)

The selected hit compounds showed ΔG scores ranging from -118.09 to -74.85 kJ/mol in both wildtype and mutant ABL1. Considering all in silico studies performed, it can be inferred that the identified molecules hold promise as potential candidates for drug design aimed at targeting CML.

16 days ago

Preclinical • Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

ABL1 T315I

16d

COVID-19 mitigates the response to TKIs in patients with CML via the inhibition of T-cell immunity. (PubMed, Front Immunol)

The results showed that the level of BCR-ABL P210 was upregulated upon transfection of SARS-CoV-2 pseudovirus into blood samples of CML patients. Our results demonstrate that COVID-19 suppresses the immune activity and consequentially elevates the level of BCR-ABL P210 of CML patients.

16 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD8 (cluster of differentiation 8)

17d

ECOG-ACRIN E1910: Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P3, N=488, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Mar 2025

17 days ago

Trial completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • IGH (Immunoglobulin Heavy Locus) • ETV6 (ETS Variant Transcription Factor 6) • CD4 (CD4 Molecule) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)

Rituxan (rituximab) • cytarabine • cyclophosphamide • etoposide IV • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • Truxima (rituximab-abbs) • mercaptopurine • Hemady (dexamethasone tablets) • Mabtas (rituximab biosimilar) • Starasid (cytarabine ocfosfate)

18d

SWOG-S1318: Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

18 days ago

Trial completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CD4 (CD4 Molecule) • CSF1R (Colony stimulating factor 1 receptor)

ABL2 fusion

dasatinib • Blincyto (blinatumomab) • methotrexate • vincristine • mercaptopurine • Xatmep (methotrexate oral solution)

19d

RAPID-CRISPR: Highly Sensitive Diagnostic Assay for Detection of PML-RARA Isoforms in Acute Promyelocytic Leukemia. (PubMed, Blood Adv)

This simple, cost-effective tool, with its easy-to-read format, is particularly valuable in under-resourced regions. The assay facilitates timely diagnosis and prompt administration of lifesaving therapies such as all-trans retinoic acid and arsenic trioxide in APL.

19 days ago

Journal • Diagnostic assay

BCR (BCR Activator Of RhoGEF And GTPase) • PML (Promyelocytic Leukemia)

PML-RARA fusion

arsenic trioxide

20d

New metal complexes of 1H-benzimidazole-2-yl hydrazones: cytostatic, proapoptotic and modulatory activity on kinase signaling pathways. (PubMed, Arch Biochem Biophys)

on key kinase signaling pathways was further studied in the ER+ breast cancer (MCF-7) and bcr-abl+ leukemic (AR-230) in vitro tumor models in a comparative manner to the reference drugs tamoxifen and imatinib, respectively. Inhibition of the JAK/STAT signaling pathway was outlined as a prominent mechanism in the antileukemic activity against the Ph+ AR-230 in vitro model, whereas recruitment and activation of the extrinsic apoptotic pathway was established in the MCF-7 cells.

20 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

imatinib • tamoxifen

20d

BCR::ABL1 deep molecular response quantification and transcript type identification in chronic myeloid leukemia using an FDA-approved droplet-based digital PCR assay. (PubMed, J Mol Diagn)

In addition, we observed that e13a2 and e14a2 BCR::ABL1 transcript types could be discriminated based on the mean fluorescence intensity of BCR::ABL1-positive droplets. BCR::ABL1 digital PCR is feasible for DMR quantification in clinical practice and offers an increased sensitivity over RT-qPCR.

20 days ago

FDA event • Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Xpert® BCR-ABL Ultra

22d

Molecular Profile of BCR-ABL1 Negative Myeloproliferative Neoplasm in a Moroccan Population. (PubMed, Asian Pac J Cancer Prev)

In conclusion, our study provides valuable insights into the prevalence and characteristics of JAK2, CALR, and MPL mutations in BCR-ABL1 negative MPNs in the Moroccan population, highlighting the importance of genetic characterization to optimize the clinical management of these diseases.

22 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • CALR (Calreticulin) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

JAK2 V617F • JAK2 mutation • CALR mutation • STAT5A mutation

23d

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 | Trial completion date: Dec 2025 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Apr 2025

23 days ago

Trial completion date • Trial primary completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Inrebic (fedratinib)

24d

Rational Approach to New Chemical Entities with Antiproliferative Activity on Ab1 Tyrosine Kinase Encoded by the BCR-ABL Gene: An Hierarchical Biochemoinformatics Analysis. (PubMed, Pharmaceuticals (Basel))

Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the top100/base (600 structures), in comparison with the commercial drug imatinib, showed that only nine exhibited the desired properties...Considering future in vitro or in vivo assays, we elaborated the theoretical synthetic routes of the promising compounds identified in the present study. Based on our in silico findings, the selected ligands show promise for future studies in developing chronic myeloid leukemia treatments.

24 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

imatinib

25d

Febuxostat enhances the efficacy of dasatinib by inhibiting ATP-binding cassette subfamily G member 2 (ABCG2) in chronic myeloid leukemia cells. (PubMed, Biomed Pharmacother)

This was achieved partially by inhibition of ABCG2-mediated excretion of dasatinib from CML cells. Therefore, these findings provide important insights for improving CML treatment and overcoming TKI resistance.

25 days ago

Journal

BCR (BCR Activator Of RhoGEF And GTPase) • ABCG2 (ATP Binding Cassette Subfamily G Member 2)

ABCG2 overexpression

dasatinib

26d

IIT PH1 KDS-1001 in Patients With CML (clinicaltrials.gov)

P1, N=0, Withdrawn, Duke University | N=12 --> 0 | Trial completion date: Sep 2027 --> Dec 2029 | Not yet recruiting --> Withdrawn | Trial primary completion date: Sep 2025 --> Dec 2027

26 days ago

Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

SAR445419

26d

Navigating diagnostic dilemmas: a rare presentation of extramedullary T-lymphoblastic leukemia/lymphoma with chronic myeloid leukemia. (PubMed, J Hematop)

This case contributes to the medical literature by documenting a rare occurrence of extramedullary T-LBL with concurrent CML. The absence of a CML history makes the diagnosis particularly challenging and underscores the need for comprehensive and personalized treatment strategies.

26 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

BCR-ABL1 fusion

Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib: A Phase 1b Randomized Clinical Trial. (PubMed, JAMA Oncol)

Olverembatinib may provide a viable new treatment option for patients after failure of 2 or more TKIs. ClinicalTrials.gov Identifier: NCT04260022.

1 month ago

Clinical • P1 data • Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

ABL1 T315I

Iclusig (ponatinib) • Scemblix (asciminib) • Nailike (olverembatinib)

Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting. (PubMed, Nat Commun)

Human data confirm that IGF1 and fibronectin staining in trephine biopsies are correlated. Our studies suggest that fibrinolysis-mediated ECM remodeling and subsequent growth factor release influence B-ALL progression and inhibition of this process by EACA may be beneficial as adjunct therapy.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IGF1 (Insulin-like growth factor 1)

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.

1 month ago

Journal • IO biomarker

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

imatinib

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.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • AURKB (Aurora Kinase B)

dasatinib • barasertib-HQPA (AZD2811) • NMI-900

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.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD34 (CD34 molecule) • DDX3X (DEAD-Box Helicase 3 X-Linked)

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.

1 month ago

Clinical • Review • Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

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

1 month ago

Trial completion date

MLL rearrangement • MLL rearrangement

dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

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.

1 month ago

Clinical

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Xpert® BCR-ABL Ultra

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.

1 month ago

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)

BCR-ABL1 fusion • MLL fusion

SureSeq™ Myeloid Fusion Panel

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).

1 month ago

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

BCR-ABL1 mutation

ipsogen BCR-ABL1 mbcr Kit

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.

1 month ago

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Xpert® BCR-ABL Ultra

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.

1 month ago

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

ABL1 fusion

Xpert® BCR-ABL Ultra

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

1 month ago

New trial

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Scemblix (asciminib)

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

1 month ago

Enrollment closed

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Inrebic (fedratinib)

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.

1 month ago

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)

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

MI Tumor Seek™

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

1 month ago

Trial completion date • Trial primary completion date

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)

Chr del(5q)

azacitidine • decitabine

2ms

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. Although muTP53 ALL achieved a higher MRD-FC negative response compared to wtTP53 ALL, this did not translate into long-term survival in the muTP53 ALL. Whether using NGS for B-cell and T-cell receptors as a method for MRD testing, like clonoSEQ®, would provide a better prognostic tool is currently unknown.

2 months ago

IO biomarker

TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

TP53 mutation • TP53 wild-type • BCR-ABL1 mutation

clonoSEQ

Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin)

2ms

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.

2 months ago

Clinical

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)

CRLF2 rearrangement • JAK2 rearrangement

clonoSEQ

Blincyto (blinatumomab)

2ms

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)

Method : 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...Conclusion : 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.

2 months ago

Clinical • Next-generation sequencing • Discordant

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)

LymphoTrack® Dx IGH Assay

doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • vincristine

2ms

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

2 months ago

Trial completion date • Trial primary completion date • Combination therapy

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

Jakafi (ruxolitinib)

2ms

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.

2 months ago

Journal

BCR (BCR Activator Of RhoGEF And GTPase) • PML (Promyelocytic Leukemia)

PML-RARA fusion

2ms

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.

2 months ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

2ms

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.

2 months ago

Retrospective data • Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

imatinib