News - ABL1 fusion - LARVOL VERI

Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with BCR::ABL1 fusion. (PubMed, EJHaem)

In conclusion, our results suggest that pre-transplant TKI could improve disease status before allo-HCT. Moreover, allo-HCT resulted in high OS, high LFS, low relapse, and low NRM rates in patients with AML with BCR::ABL1.

7 days ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

17d

Discontinuation of tyrosine kinase inhibitors before epiphyseal closure leading to improved short stature in pediatric chronic myelogenous leukemia (PubMed, Rinsho Ketsueki)

Due to intolerance, the tyrosine kinase inhibitor (TKI) was changed from imatinib to dasatinib to nilotinib. Growth suppression by TKIs is a problem in the management of pediatric CML. This case illustrates how improvement in severe short stature can be achieved by discontinuing TKI therapy before epiphyseal closure.

17 days ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

dasatinib • imatinib • Tasigna (nilotinib)

Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion (PubMed, Zhonghua Xue Ye Xue Za Zhi)

In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PHF6 (PHD Finger Protein 6)

NPM1 mutation • RUNX1 mutation • ASXL1 mutation • PHF6 mutation • ABL1 fusion

The first case of six-way complex translocation of t(4;7;9;22;8;14) in a patient with chronic myeloid leukemia. (PubMed, J Hematop)

After treatment with imatinib for 4 months, the patient achieved complete cytogenetic response (CCyR) and early molecular response (EMR). This is the first report of complex chromosomal karyotype involving six-way translocation in CML; the combination of chromosome analysis and FISH techniques is an effective strategy in determining the karyotype result.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

imatinib

ERG and c-MYC regulate a critical gene network in BCR::ABL1-driven B cell acute lymphoblastic leukemia. (PubMed, Sci Adv)

Profiling of ERG- and c-MYC-dependent gene expression and analysis of ChIP-seq data established ERG and c-MYC coordinate a regulatory network in BCR::ABL1 B-ALL that controls expression of genes involved in several biological processes. Prominent was control of ribosome biogenesis, including expression of RNA polymerase I (POL I) subunits, the importance of which was validated by inhibition of BCR::ABL1 cells by POL I inhibitors, including CX-5461, that prevents promoter recruitment and transcription initiation by POL I. Our results reveal an essential ERG- and c-MYC-dependent transcriptional network involved in regulation of metabolic and ribosome biogenesis pathways in BCR::ABL1 B-ALL, from which previously unidentified vulnerabilities and therapeutic targets may emerge.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ERG (ETS Transcription Factor ERG)

MYC expression • ABL1 fusion

pidnarulex (CX-5461)

2ms

Characteristics and literature review of ETV6::ABL1 fusion gene-positive acute myeloid leukemia. (PubMed, Int J Hematol)

ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative.

2 months ago

Review • Journal

ABL1 (ABL proto-oncogene 1) • ETV6 (ETS Variant Transcription Factor 6)

ABL1 fusion • ETV6-ABL1 fusion

dasatinib

2ms

Chronic Myeloid Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. (PubMed, J Natl Compr Canc Netw)

Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase-CML.

2 months ago

Clinical guideline • NCCN guideline • Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

2ms

Quantitative detection of T315I mutations of BCR::ABL1 using digital droplet polymerase chain reaction. (PubMed, Hematol Transfus Cell Ther)

T315I mutations have a high incidence in Ph-positive ALL patients even if the course of disease is short. In molecular biology, T315I mutation detection is indicated for CML patients not in remission.

2 months ago

Journal • Polymerase Chain Reaction • Tumor mutational burden

TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1)

ABL1 T315I • ABL1 fusion

3ms

Novel Four-Way Variant Translocation, t(1;9;22;16)(q21;q34;q11.2;q24), in a Patient with Chronic Myeloid Leukemia. (PubMed, Diagnostics (Basel))

Nested RT-PCR of the BCR::ABL1 gene revealed a major BCR::ABL rearrangement. The treatment with nilotinib achieved a complete hematologic, cytogenetic, and molecular response after 12 months.

3 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

Tasigna (nilotinib)

3ms

e14a2 Transcript Favors Treatment-Free Remission in Chronic Myeloid Leukemia When Associated with Longer Treatment with Tyrosine Kinase Inhibitors and Sustained Deep Molecular Response. (PubMed, J Clin Med)

This study aimed to determine the effect of transcript type on TFR in patients receiving frontline treatment with imatinib (IM) or second-generation TKI (2G-TKI)...In addition, cases with the e14a2 transcript type treated at least 119 months with IM presented a better TFR (p = 0.024). On the other hand, the type of transcript did not affect the cytogenetic or molecular response in 2G-TKI treated patients; however, the use of 2G-TKI may be associated with higher and earlier DMR in patients with the e14a2 transcript.

3 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

imatinib

3ms

Erythroid variant evolving from chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitors: a rare case report. (PubMed, Diagn Pathol)

The erythroid variant of CML is distinguished by the presence of t(9;22) (q34;q11.2) BCR::ABL1 in predominant erythroid precursors at different stages of maturation. In a myeloid neoplasm showing predominant erythroid hyperplasia without typical CML features, it is vital to correlate morphology and t(9;22) BCR::ABL1 cytogenetic testing for accurate diagnosis, and to prevent confusion with PEL transformation in CML.

3 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

3ms

Establishment of the Myeloid TBX-Code Reveals Aberrant Expression of T-Box Gene TBX1 in Chronic Myeloid Leukemia. (PubMed, Int J Mol Sci)

TBX1 forms an integral part of an oncogenic regulatory network impacting proliferation, survival, and differentiation. Thus, the data spotlight novel diagnostic markers and potential therapeutic targets for this malignancy.

3 months ago

Journal

ABL1 (ABL proto-oncogene 1) • FGF2 (Fibroblast Growth Factor 2) • MIR17HG (MiR-17-92a-1 Cluster Host Gene) • GATA1 (GATA Binding Protein 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MIR92A1 (MicroRNA 92a-1) • TBX1 (T-Box Transcription Factor 1)

ABL1 fusion

dasatinib • imatinib

4ms

Exploration of treatment-free remission in CML, based on molecular monitoring. (PubMed, Cancer Med)

Currently, predictive indicators for treatment-free remission outcomes and recurrence are lacking in clinical practice. In future, treatment-free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment-free remission.

4 months ago

Review • Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

5ms

Combinatorial treatment options for highly resistant compound mutations in the kinase domain of the BCR::ABL1 fusion gene in Ph-positive leukemias. (PubMed, Am J Hematol)

No abstract available

5 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

5ms

PARP1 Characterization as a Potential Biomarker for BCR::ABL1 p190+ Acute Lymphoblastic Leukemia. (PubMed, Cancers (Basel))

In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of BCR::ABL1 p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. Overall, we demonstrate the effectiveness of PARPi in the treatment of BCR::ABL1 p190+ ALL cell models and that PARP1 is differentially expressed in patient samples. We hope our findings help expand the characterization of molecular profiles in ALL settings and guide future investigations into novel biomarker detection and pharmacological choices in clinical practice.

5 months ago

Journal • PARP Biomarker

ABL1 (ABL proto-oncogene 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1)

ABL1 fusion

imatinib • AZD2461

5ms

Chronic myeloid leukemia with sleep-related painful erections as a first symptom: a case report. (PubMed, J Med Case Rep)

We considered that the occurrence of sleep-related painful erections was related to chronic myeloid leukemia and the case might be secondary sleep-related painful erections.

5 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

5ms

A Real-World Single-Center Report on the Effectiveness and Safety of Blinatumomab Treatment on Pediatric Acute Lymphoblastic Leukemia in China (ASH 2023)

Blinatumomab is an effective treatment for B-ALL MRD cleanup with a good safety profile. It may, however, not benefit patients with R/R B-ALL with high tumor loads before blinatumomab, and those who carry BCR: : ABL1 fusion gene. Studies with a larger sample size are needed to confirm the results.

5 months ago

Clinical • Real-world evidence • Real-world

ABL1 (ABL proto-oncogene 1) • CD19 (CD19 Molecule)

CD19 expression • ABL1 fusion

Blincyto (blinatumomab)

5ms

ETV6-ABL1 Fusion Gene Was Associated with a Poor Prognosis in Patients with Acute Myeloid Leukemia (ASH 2023)

All there patients received the same IA regimen(idarubicincytarabine) as induction chemotherapy and achieved complete remission, followed by multi-agent chemotherapy as consolidation treatment...1 received additional targeted therapy with sorafenib... ETV6-ABL1 fusion gene is a rare but recurrent genetic aberration in AML, and its rearrangement is not uniform across eachpatient, typically involving cryptic insertions. Routine chromosome G-banding analysis may not identify this fusion gene, and the combined use of fluorescence in situ hybridization and PCR is recommended for better detection for ETV6-ABL1. Patients with this fusion gene have a high relapse rate and a poor prognosis.

5 months ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • ETV6 (ETS Variant Transcription Factor 6) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)

FLT3-ITD mutation • ABL1 fusion • ETV6-ABL1 fusion • NUP98-NSD1 fusion

dasatinib • sorafenib • idarubicin hydrochloride

5ms

The Efficacy and Safety of Olverembatinib Combined with Monoclonal Antibodies As Salvage Therapy for RR B ALL with ABL1 Fusion Gene Positive (ASH 2023)

Recently, such pts have new hope with the wide application of a novel third-generation TKI Olverembatinib developed in China and Blinatumomab（CD19 antibody,BITE）and INOTUZUMAB OZOGAMICIN(CD22 antibody,Ino. For heavily treated RR ABL1+B ALL pts,including those after treatment with ponatinib and other TKICART and HSCT, Olverembatinib combined with monoclonal antibodies is effective and safe. In my cases, it is particularly noteworthy that one pts ,Ph like ALL with ABL1 FG, received Olverembatinib combination BITE and achieved a surprising response, so Olverembatinib may also be effective and safe for such pts. In addition, venetoclax may be used as a sensitizer for TKI or other antitumor drugs.

5 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD22 (CD22 Molecule)

CD19 expression • ABL1 T315I • CD22 expression • ABL1 fusion

Venclexta (venetoclax) • Iclusig (ponatinib) • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Nailike (olverembatinib)

5ms

T cell phenotype and lack of eosinophilia are not uncommon in extramedullary myeloid/lymphoid neoplasms with ETV6::FLT3 fusion: a case report and review of the literature. (PubMed, Virchows Arch)

Here, we report a very unusual case of myeloid/lymphoid neoplasm with ETV6::FLT3 fusion with a nodal presentation without associated eosinophilia. Our case draws attention to diagnostic pitfalls in these rare entities.

5 months ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6)

FGFR1 fusion • ABL1 fusion • ETV6-ABL1 fusion

5ms

BCR::ABL1 fusion gene positive de novo acute myeloid leukemia with coexistence of NRAS mutation and presented with a peculiar CD58 positive immunophenotype. (PubMed, Cytometry B Clin Cytom)

No abstract available

5 months ago

Journal

ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CD58 (CD58 Molecule)

NRAS mutation • ABL1 fusion

6ms

Philadelphia-like B-Cell Acute Lymphoblastic Leukemia in a Largely Hispanic Population: Disease Features and Outcomes in the Era of Immunotherapy a Single Institutional Study (ASH 2023)

Compared to Ph-negative, Ph-like patients were more likely to have a refractory disease (20.6% vs. 6.2% P=0.006) and require Blinatumomab (67.2% vs. 39.3% P<0.001), with a non-significant trend towards lower rates of CR (84.1% vs 90.9% P=0.21)... Ph-like B- Cell ALL represents a high-risk disease subtype of adult B-ALL, with poor EFS and frequent treatment failure. CRLF2 translocation confers worse CIR and EFS within Ph-like patients and requires novel treatment approaches.

6 months ago

Clinical • IO biomarker

ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • PAX5 (Paired Box 5) • P2RY8 (P2Y Receptor Family Member 8)

CRLF2 rearrangement • ABL1 fusion • CRLF2 mutation • EPOR rearrangement

Blincyto (blinatumomab)

6ms

Updated Results from a Phase II Study of Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia (ASH 2023)

Pts received hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...One pt discontinued blinatumomab due to a related adverse event (grade 2 encephalopathy and dysphasia). No pts discontinued INO due to toxicity, and no cases of veno-occlusive disease have been observed.

6 months ago

Clinical • P2 data

TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • NUP214 (Nucleoporin 214)

TP53 mutation • KMT2A rearrangement • MLL rearrangement • TP53 expression • CRLF2 overexpression • NUP214-ABL1 fusion • ABL1 fusion

Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV

6ms

Feasibility and Outcome of Post-Induction Therapy Incorporating Dasatinib for Patients with Newly Diagnosed ABL-Class Fusion B-Lymphoblastic Leukemia (ABL-class Fusion B-ALL): Children's Oncology Group AALL1131 (ASH 2023)

These patients are predicted to be sensitive to ABL-class tyrosine kinase inhibitors, such as imatinib or dasatinib. Patients with ABL-class fusions were more likely male, EOI MRD+, and had poorer outcomes. Seventy-seven percent of patients enrolled on the Dasatinib arm did not complete prescribed therapy. While dasatinib was well tolerated, treatment failures occurred early, indicating alternate strategies are needed.

6 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ABL2 (ABL Proto-Oncogene 2, Non-Receptor Tyrosine Kinase) • CSF1R (Colony stimulating factor 1 receptor)

ABL2 fusion • ABL1 fusion • CSF1R fusion

dasatinib • imatinib

6ms

Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)

1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.

6 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation

6ms

Distinct Pattern of ABL1 Genomic Breakpoints in Chronic Myeloid Leukemia and BCR::ABL1-Positive Acute Lymphoblastic Leukemia: Analysis of 884 Patients with Minor and Major BCR::ABL1 Fusion (ASH 2023)

Supported by AZV (NU21-03-00128) and NICR No. LX22NPO5102.

6 months ago

Clinical

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

6ms

RNA Fusions and Their Association with DNA Alterations in Myeloid Neoplasia Patients Identified By a Single Tube Multimodal Comprehensive Genomic Profiling Test (ASH 2023)

A robust low-noise RNA fusion detection assay coupled us DNA alterations on myeloid disorders in a single assay enables to fully molecularly characterize acute myeloid leukemias and other myeloid disorders. Frequencies of well-known fusions in a small community-based cohort were similar to studies performed in academic settings with subsets of gene alterations being mutually exclusive from fusions. Larger studies are needed to confirm those associations.

6 months ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • NPM1 (Nucleophosmin 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • CCND2 (Cyclin D2) • PHF6 (PHD Finger Protein 6) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • ZNF384 (Zinc Finger Protein 384)

FGFR1 fusion • ABL1 fusion • PDGFRA fusion

6ms

Continuous therapy response references for BCR::ABL1 monitoring in pediatric chronic myeloid leukemia. (PubMed, Sci Rep)

By further comparing BCR::ABL1 transcript levels with BCR::ABL1 fusion gene copy numbers, it is also possible to model the differential dynamics of BCR::ABL1 expression and cell number under therapy. The developed methodology can be transferred to other biomarkers for continuous therapy monitoring.

6 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 expression • ABL1 fusion

6ms

Deciphering Potential Molecular Signatures to Differentiate Acute Myeloid Leukemia (AML) with BCR::ABL1 from Chronic Myeloid Leukemia (CML) in Blast Crisis. (PubMed, Int J Mol Sci)

Finally, the hypothesis of AML with BCR::ABL1 arising from driver mutations on a BCR::ABL1 background behaving as a clonal hematopoiesis mutation is discussed. Validation of our data in larger cohorts and basic research are needed to better understand the molecular and cellular aspects of AML with a BCR::ABL1 entity.

6 months ago

Journal

ABL1 (ABL proto-oncogene 1) • IL2RA (Interleukin 2 receptor, alpha)

ABL1 fusion • IL2R overexpression

8ms

Histone demethylase PHF8 facilitates the development of chronic myeloid leukaemia by directly targeting BCR::ABL1. (PubMed, Br J Haematol)

Furthermore, the proliferation-inhibited function of PHF8-knockdown have stronger effect on imatinib mesylate (IM)-resistant CML cells. Mechanistically, we identified that PHF8 as a transcriptional modulator interacted with the promoter of the BCR::ABL1 fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting BCR::ABL1 transcription. Overall, our study suggests that targeting PHF8, which directly regulates BCR::ABL1 expression, is a useful therapeutic approach for CML.

8 months ago

Journal • Epigenetic controller

ABL1 (ABL proto-oncogene 1)

ABL1 expression • ABL1 fusion

imatinib

8ms

ZMIZ1-ABL1 Fusion, an Uncommon Molecular Event With Clinical Implications in Pediatric Cancer (CAP 2023)

Treatment with the tyrosine kinase inhibitor, imatinib, was [VGH1] implemented and effective, yielding no evidence of disease in the marrow at day 29 postinduction... t(9;10) translocations resulting in a mutant ZMIZ1-ABL1 fusion transcript are an ultrarare form of Philadelphia chromosome–like ALL. Although the karyotype was complex, identifying the t(9;10)(q34;q22) translocation, the disruption of ABL1 by FISH, and the ZMIZ1-ABL1 mutant transcript provided an avenue for an effective treatment by targeting ABL1. Our data support the use of tyrosine kinase inhibitors to treat ZMIZ1-ABL1–derived B-cell ALL.

8 months ago

Clinical

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

imatinib

8ms

BCR::ABL1-Positive (Ph+) T-Lymphoblastic Leukemia/Lymphoma With Concurrent Chronic Myeloid Leukemia: Report of 2 Cases With Additional MECOM Rearrangement in 1 Case (CAP 2023)

The patient in case 1 received standard chemotherapy for T-ALL/LBL, plus dasatinib, with pretransplantation biopsy showing BCR::ABL1 fusion transcript at 1.71% international scale and rare cells, by cytogenetics, showing BCR::ABL1 and ETV6 rearrangements (negative MECOM rearrangement). To our knowledge, case 1 is the first reported adult case with a MECOM rearrangement in concurrently diagnosed T-ALL/LBL and CML (previously reported in the pediatric setting). The above rare cases of T-ALL/LBL and concurrent CML highlight the importance of a comprehensive clinical and laboratory evaluation to fully elucidate a patient’s disease status in the context of CML.

8 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • ETV6 (ETS Variant Transcription Factor 6) • MECOM (MDS1 And EVI1 Complex Locus)

MECOM rearrangement • ABL1 fusion

dasatinib

8ms

Updates on Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (SOHO 2023)

Introduction Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) was historically associated with poor outcomes when treated with chemotherapy followed by allogeneic stem cell transplantation (ASCT).1 Four different BCR::ABL1 tyrosine kinase inhibitors (TKIs) have been combined with chemotherapy in patients with Ph-positive ALL, leading to improved outcomes: imatinib, dasatinib, nilotinib, and ponatinib...Future studies combining asciminib or olverembatinib with blinatumomab in the frontline setting are warranted...These strategies have reduced the incidence of toxicities and mitigated the need for ASCT. The incorporation of NGS for the detection of MRD can help select patients who may be candidates for TKI discontinuation.

8 months ago

IO biomarker

ABL1 (ABL proto-oncogene 1) • SLC1A5 (Solute Carrier Family 1 Member 5)

ABL1 T315I • ABL1 fusion

dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Blincyto (blinatumomab) • Scemblix (asciminib) • Nailike (olverembatinib)

8ms

Amplification of the BCR::ABL1 Fusion Gene: A Rare Phenomenon in B-cell Acute Lymphoblastic Leukemia. (PubMed, Turk J Haematol)

No abstract available

8 months ago

Journal

ABL1 (ABL proto-oncogene 1)

ABL1 fusion

8ms

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions: reevaluation of the defining characteristics in a registry-based cohort. (PubMed, Leukemia)

The comparison between patients with PDGFRA/PDGFRB vs. FGFR1, JAK2, and ETV6::ABL1 fusion genes revealed a similar occurrence of primary BP (17/104, 16% vs. 8/31 26%, p = 0.32), a lower frequency (5/87, 6% vs. 8/23, 35%, p = 0.003) of and a later progression (median 87 vs. 19 months, p = 0.053) into secondary BP, and a better overall survival from diagnosis of BP (17.1 vs. 1.7 years, p < 0.0008). We conclude that hypereosinophilia with or without monocytosis and various phenotypes of BP occur at variable frequencies in MLN-TK.

8 months ago

Journal

ABL1 (ABL proto-oncogene 1) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FGFR1 fusion • ABL1 fusion • ETV6-ABL1 fusion • JAK2 fusion