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    GENE:

    ABL1 (ABL proto-oncogene 1)

    i
    Other names: ABL proto-oncogene 1, ABL, c-ABL, JTK7, p150, ABL1
    2d
    CD56briCD38+ as a novel neutrophil-specific marker in chronic myeloid leukemia. (PubMed, Heliyon)
    Moreover, this increase disappears in CML patients after treatment with tyrosine kinase inhibitors when the curative effect was satisfactory. We conclude that an increase in the proportion of CD56briCD38+ neutrophil subsets exceeding 2.0 % of total neutrophils serves as a highly sensitive and specific flow cytometry marker, enabling rapid and accurate identification of CML.
    Journal • IO biomarker
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    ABL1 (ABL proto-oncogene 1) • CD38 (CD38 Molecule) • NCAM1 (Neural cell adhesion molecule 1)
    |
    BCR-ABL1 fusion • CD38 expression • NCAM1 expression
    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
    |
    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)
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    BCL2 expression • MYC expression • TP53 expression • BAX expression
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    imatinib
    5d
    Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells. (PubMed, Korean J Physiol Pharmacol)
    Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi-target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
    Journal
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    ABL1 (ABL proto-oncogene 1)
    |
    imatinib • mebendazole
    5d
    Results of the prospective EORTC Children Leukemia Group study 58081 in precursor B- and T-cell acute lymphoblastic leukemia. (PubMed, Hemasphere)
    Dexamethasone (DXM) was used in average-risk 2 (AR2) T-ALL and B-ALL during induction, 10 and 6 mg/m2/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high-dose methotrexate, and a postconsolidation MRD time point was added to stratify patients...The HR was 2.15 (99% CI: 0.67-6.85) for very low-risk but 0.34 (99% CI: 0.13-0.89) for AR2. The particularly favorable results observed in the T-ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.
    Journal
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    ABL1 (ABL proto-oncogene 1)
    |
    methotrexate • dexamethasone • leucovorin calcium • methotrexate IV
    5d
    Dose Modifications in the Management of Chronic Phase Chronic Myeloid Leukemia: Who, What, and When. (PubMed, J Natl Compr Canc Netw)
    Additionally, emerging therapeutics such as the new class of BCR::ABL1 allosteric inhibitors are under evaluation with a goal of improving tolerability. However, with many TKIs on the cusp of becoming generic, dose reduction becomes an appealing and important cost-effective strategy to minimize TEAEs and improve quality of life while preserving outstanding outcomes in CP-CML.
    Review • Journal
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    ABL1 (ABL proto-oncogene 1)
    6d
    Efficacy and Safety of the First-in-Class STAMP-Inhibitor Asciminib in Patients With Chronic Myeloid Leukemia. (PubMed, Clin Lymphoma Myeloma Leuk)
    Asciminib was found to have excellent efficacy and safety therapeutic profiles. The lack of comprehensive reviews about asciminib, thus, the current study aimed to evaluate the clinical and preclinical evidence of the efficacy and safety of asciminib.
    Review • Journal
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    ABL1 (ABL proto-oncogene 1)
    |
    Scemblix (asciminib)
    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)
    6d
    Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology. (PubMed, J Thromb Thrombolysis)
    Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.
    Retrospective data • Journal • Real-world evidence • Real-world
    |
    ABL1 (ABL proto-oncogene 1)
    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)
    |
    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
    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
    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)
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    Xpert® BCR-ABL Ultra
    8d
    Evaluation of OGT's SureSeq Myeloid Fusion Complete NGS Workflow Solution V2 for Partner-Agnostic Fusion Gene Detection in Acute Leukemias (AMP 2024)
    We demonstrated the capability of OGT's SureSeq Myeloid Fusion Complete NGS Workflow Solution V2 to achieve 100% accurate detection for novel and canonical translocations. By allowing concurrent detection of multiple known and novel rearrangements, NGS assays offer an economical and efficient alternative to routine cytogenetic approaches.
    Next-generation sequencing
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    ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • HOXD8 (Homeobox D8)
    |
    KMT2A rearrangement • MLL rearrangement
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    SureSeq™ Myeloid Fusion Panel
    8d
    Detection of Chronic Myeloid Leukemia Resistance with DNA Sequencing from Dried Blood Spots (AMP 2024)
    This project highlights the application of creative and robust methods of molecular diagnostics for LMICs, allowing for the treatment and monitoring of patients with previously limited access to assays and medications widely available in Western industrialized countries.
    ABL1 (ABL proto-oncogene 1)
    |
    ABL1 T315I • ABL1 Y253H
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    Oncomine Myeloid Assay GX
    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
    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)
    11d
    A prospective clinical study to evaluate the efficacy of dexitabine in maintenance therapy after hematopoietic stem cell transplantation in juvenile myelomonocytic leukemia (ChiCTR2400091166)
    P=N/A, N=40, Not yet recruiting, The Seventh Affiliated Hospital, Sun Yat-sen University; The Seventh Affiliated Hospital, Sun Yat-sen University
    New trial
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    KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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    KRAS mutation • NRAS mutation • NF1 mutation • PTPN11 mutation • CBL mutation
    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)
    |
    Chr del(5q)
    |
    azacitidine • decitabine
    15d
    A mechanism for hypoxia-induced inflammatory cell death in cancer. (PubMed, Nature)
    Reconstitution studies with RNF213 mutants confirm that the RZ domain mediates tumour cell death. In concert, our results identify a unique, potentially targetable PTP1B-RNF213-CYLD-SPATA2 pathway critical for the control of inflammatory cell death in hypoxic tumours, provide new insights into RNF213 regulation and have potential implications for the pathogenesis of Moyamoya disease, inflammatory disorders and autoimmune disease.
    Journal • Inflammatory cell
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    HER-2 (Human epidermal growth factor receptor 2) • ABL1 (ABL proto-oncogene 1) • PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1) • NLRP3 (NLR Family Pyrin Domain Containing 3)
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    EGFR positive
    15d
    Immune checkpoints PD1/PDL1, TIM3/GAL9 and key immune mediators landscape reveal differential expression dynamics on imatinib response in chronic myeloid leukemia. (PubMed, Ann Hematol)
    Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • ABL1 (ABL proto-oncogene 1) • PD-1 (Programmed cell death 1) • IL6 (Interleukin 6) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL2 (Interleukin 2) • FOXP3 (Forkhead Box P3) • GATA3 (GATA binding protein 3) • IL4 (Interleukin 4)
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    IL2 expression • FOXP3 expression
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    imatinib
    15d
    Single-cell multiomics analysis of chronic myeloid leukemia links cellular heterogeneity to therapy response. (PubMed, Elife)
    In addition, we found the ratio of LSC/HSC to be higher in patients with prospective treatment failure compared to optimal responders, at diagnosis as well as following 3 months of TKI therapy. Collectively, this data builds a framework for understanding therapy response and adapting treatment by devising strategies to extinguish or suppress TKI-insensitive LSCs.
    Retrospective data • Journal
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    ABL1 (ABL proto-oncogene 1) • CR1 (Complement C3b/C4b Receptor 1) • DPP4 (Dipeptidyl Peptidase 4)
    15d
    Mechanistic Learning Reveals the Reciprocal Cell Fate Transitions That Drive Disease Progression in B-Cell Acute Lymphoblastic Leukemia (ASH 2024)
    Stem reciprocity is predictive of disease state, BCR::ABL1 status and MRD status. Our findings highlight the potential of mechanistic learning in enhancing both the understanding and predictive accuracy of disease progression.
    IO biomarker
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    ABL1 (ABL proto-oncogene 1) • CD34 (CD34 molecule)
    |
    clonoSEQ
    15d
    Comprehensive Genomic Profiling (CGP) of Acute Lymphoblastic Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)
    This analysis of 2,637 samples comprising a variety of molecular subtypes of ALL demonstrated that the F1H assay detects pathogenic genomic alterations with diagnostic, prognostic, and therapeutic significance. As both the treatment landscape and disease classification system in ALL have continued to evolve over time, CGP assays such as F1H can play a critical role in clinical decision making by simultaneously assessing the presence and absence of numerous actionable genomic alterations and biomarkers with a single assay.
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • PBX1 (PBX Homeobox 1) • ABL2 (ABL Proto-Oncogene 2, Non-Receptor Tyrosine Kinase)
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    TP53 mutation • KRAS mutation • NRAS mutation • PTEN mutation • CDKN2A deletion
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    FoundationOne® Heme CDx
    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)
    |
    TP53 mutation • TP53 wild-type • BCR-ABL1 mutation
    |
    clonoSEQ
    |
    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)
    |
    CRLF2 rearrangement • JAK2 rearrangement
    |
    clonoSEQ
    |
    Blincyto (blinatumomab)
    15d
    Clearance of Very Low Levels of Measurable Residual Disease with Blinatumomab Significantly Improves Outcomes in B-Cell Acute Lymphoblastic Leukemia (ASH 2024)
    Non-responders to blinatumomab have poor outcomes (2-year RFS: 25%) but may be salvaged by ASCT. The relatively low rate of NGS MRD negativity with blinatumomab monotherapy (31% in Ph- B-ALL) highlights the need for combination therapies in B-ALL.
    IO biomarker
    |
    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    TP53 mutation
    |
    clonoSEQ
    |
    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)
    |
    LymphoTrack® Dx IGH Assay
    |
    doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • vincristine
    15d
    Measurable Residual Disease Monitoring for Philadelphia Positive Acute Lymphoblastic Leukemia (Ph+ALL) in the Setting of the Gimema ALL2820 Trial (ASH 2024)
    Samples derived from cases from both the experimental and the control arm, based respectively on ponatinib followed by blinatumomab and on a combination of imatinib and conventional chemotherapy. While some groups reported a higher predictive prognostic power of IG/TR monitoring, our findings do not confirm these data, also in view of the very low rate of relapses so far observed. Nevertheless, a double-hit strategy may be informative for MRD monitoring and possibly for the distinction between typical/lymphoid Ph+ ALL vs multilineage/CML-like Ph+ ALL.
    IO biomarker
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    ABL1 (ABL proto-oncogene 1) • IKZF1 (IKAROS Family Zinc Finger 1)
    |
    ABL1 fusion
    |
    LymphoTrack® Dx IGH Assay • LymphoTrack® Dx IGK Assay
    |
    imatinib • Iclusig (ponatinib) • Blincyto (blinatumomab)
    15d
    Safe and Effective Combination of Donor-Derived, Allogeneic CD19/CD22-CAR T Cells with Myeloablative Graft-Engineered Allo-HCT for High-Risk B-ALL (ASH 2024)
    Myeloablative conditioning with cyclophosphamide and total body irradiation precede infusion of investigational Orca-T, which consists of infusions of HSPCs and Tregs on Day 0 and an infusion of T conventional (Tcon) cells on Day 2. Here, we report very promising initial feasibility, safety and efficacy of the combination of allogeneic CD19/CD22-CAR T cells with Orca-T in patients with high-risk B-ALL. This paradigm shifting combination of allogeneic CAR T and allo-HCT resulted in 100% MRD- CR with full donor chimerism but without GVHD or severe CAR-mediated toxicity. These data, which demonstrate antigen-specific anti-tumor benefit of allogeneic CAR T cells in combination with GVHD prophylaxis mediated by Tregs and tacrolimus, have potential implications that could benefit patients with other hematologic diseases.
    CAR T-Cell Therapy • IO biomarker
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    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • CD22 (CD22 Molecule)
    |
    TP53 mutation
    |
    clonoSEQ
    |
    cyclophosphamide • Orca-T • firicabtagene autoleucel (CRG-022)
    16d
    Comparing de novo chronic myeloid leukemia in blastic phase with Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation. (PubMed, Cancer)
    Considering previous reports that showed inferior outcomes for de novo CML-BP compared to Ph-positive ALL, the data suggested that allogeneic HCT could overcome the poor prognosis of de novo CML-BP. These findings highlight the importance of distinguishing de novo CML-BP from Ph-positive ALL.
    Journal
    |
    ABL1 (ABL proto-oncogene 1)
    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
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Jakafi (ruxolitinib)
    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
    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
    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
    22d
    Current myeloproliferative neoplasm scoring systems for clinical practice. (PubMed, Blood)
    Here, we provide an overview of MPN disease evolution associated events incidence and conduct an exhaustive comparative review of the scoring systems currently available for each risk. Finally, we propose an algorithm for the use of these scores in clinical practice in each MPN subtype.
    Journal
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    ABL1 (ABL proto-oncogene 1)
    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
    Philadelphia chromosome-positive or Philadelphia chromosome-like B-cell precursor acute lymphoblastic leukemia with multilineage involvement in pediatric patients: a report of two cases and literature review. (PubMed, Pharmacogenet Genomics)
    This report presents two pediatric ALL cases (one Ph+ and one Ph-like) with minimal residual disease negativity established by multicolor flow cytometry but persistent transcript detection by quantitative PCR (qPCR) even after second-line treatment with tyrosine kinase inhibitors combined with blinatumomab immunotherapy. Using droplet digital PCR, BCR::ABL1 or TPM3::PDGFRB transcripts were identified in CD19+ cells as well as in non-CD19+ cells, suggesting the presence of a Ph+ or Ph-like ALL-M subtype originating from hematopoietic stem cells. This report provides information for better characterization, diagnosis, and treatment of these ALL subtypes.
    Review • Journal • IO biomarker
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    ABL1 (ABL proto-oncogene 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • TPM3 (Tropomyosin 3)
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    Blincyto (blinatumomab)