ABL1 fusion

P2, N=45, Not yet recruiting, University Health Network, Toronto

Introduction of tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 fusion protein has revolutionized frontline therapy, with successive generations of TKIs-from imatinib to dasatinib and most recently ponatinib-achieving progressively deeper and more durable molecular responses. Concurrently, the integration of immunotherapy, particularly blinatumomab, has enabled chemotherapy-sparing approaches further improving tolerability and efficacy...Treatment-free remission strategies following prolonged TKI maintenance in non-transplant patients, and the integration of chimeric antigen receptor (CAR) T-cell therapy as bridge, consolidation, or salvage, represent emerging frontiers. This review critically examines the contemporary role of allogeneic HCT in Ph+ ALL and provides a framework for transplant decision-making in the contemporary era of targeted and cellular immunotherapy.

The genetic changes included GOF mutations (KRAS, BRAF genes, etc.), LOF mutations (STAG1, SMARCA2 genes, etc.), gene fusions (BCR-ABL1, PAX3-FOXO1, etc.), and amplification (CPM, BEST3, etc.). Therefore, many different molecular mechanisms act as predictors of tumor cell response to inhibition of supertarget genes.

Initial treatment included hydroxyurea and dasatinib; however, after chronic-phase CML was confirmed, therapy was transitioned to imatinib, resulting in resolution of B symptoms, normalization of WBC counts, and reduced leg swelling. This case underscores the importance of distinguishing CEH from aggressive disease states, such as blast-phase CML or myeloid sarcoma, through comprehensive histopathological and immunohistochemical analysis.

In the multivariate analysis, WBC > 70,000/L at diagnosis (p = 0.01), p210 BCR::ABL1 fusion (p < 0.001) and monosomy 7 (p = 0.007) were independently associated with failure to achieve CMR, while use of ponatinib or dasatinib (p = 0.008) and intensive chemotherapy (IC) (p = 0.009) predicted higher CMR. vs. 149.3 months, p = 0.07) with or without allogeneic hematopoietic cell transplantation (allo-HCT). These findings suggest that allo-HCT may be deferred in selected patients achieving early CMR, although prospective validation is needed.

This case highlights a rare cytogenetic abnormality in CML characterized by acquired pericentric inversion of the derivative chromosome 9 associated with BCR and ABL1 codeletion. Such complex rearrangements likely reflect clonal evolution and may be associated with suboptimal response to first line imatinib therapy. Accurate discrimination between constitutional and acquired inv(9), together with detailed assessment of derivative chromosome 9 integrity, is essential for prognostic stratification. Comprehensive cytogenetic and molecular analyses remain critical for identifying uncommon secondary abnormalities that may influence therapeutic response and clinical outcome in CML.

Notably, during treatment with tyrosine kinase inhibitors (TKIs), she became intolerant to first- and second-generation TKIs, including the branded and generic imatinib, nilotinib, and dasatinib, followed by progression into lymphoid blast phase. This case highlights the diagnostic challenges and therapeutic complexity of managing CML in the setting of multi-TKI intolerance. Importantly, it underscores the persistent molecular silence despite repeated RT-qPCR testing and the successful introduction of asciminib as a novel therapeutic alternative.

P1/2, N=20, Recruiting, Princess Maxima Center For Pediatric Oncology

The introduction of imatinib in the early 2000s revolutionized CML treatment, transforming a fatal disease into a chronic condition with near-normal life expectancy for most patients...Emerging therapies such as vamotinib, KF1601, and combination regimens are being explored. Furthermore, new insights into non-kinase functions of BCR::ABL1 and the role of microRNAs in resistance open additional therapeutic avenues. This review provides a concise overview of CML from a historical and molecular perspective, highlighting diagnostic advances, evolving response criteria, and future directions in treatment.

P1, N=30, Recruiting, Andrew E. Place, MD | Active, not recruiting --> Recruiting | N=13 --> 30 | Trial completion date: Jul 2028 --> Jul 2030 | Trial primary completion date: Jul 2026 --> Jul 2028

In Japan, five agents-imatinib (Glivec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), and STAMP inhibitor asciminib (Scemblix®)-are currently approved for first-line therapy. Looking forward, immunologic determinants of TFR and novel therapeutic approaches, including targeting CML stem cells with agents such as asciminib or demethylating drugs, may offer prospects for cure. This review summarizes the current evidence and practical considerations in selecting first-line therapy for chronic-phase CML, with a focus on optimizing long-term outcomes and advancing toward individualized and potentially curative strategies.

TFR patients exhibited distinct enrichment in complement and coagulation cascades (C3, C4B, F9, F11) and metabolic pathways. Plasma EV proteomes reflect CML clinical status, revealing immune and cytoskeletal alterations associated with treatment response, remission, and resistance, suggesting potential biomarkers for disease monitoring.