This may be due to late presentation and poor adherence to imatinib which needs further investigations. To improve the survival of patients with CML in Rwanda, access to all available lines of TKI and better follow-up should be considered.

We systematically deconstructed the molecular subtypes of primary GISTs by integrated genomic and transcriptomic analysis. A specific GIST subtype characterized by poor treatment responses and prognosis, marked by the activation of aerobic metabolism and HRD features, may be a potential candidate for PARP inhibitors.

P1/2, N=34, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jun 2026 --> Sep 2027

The patient received high-dose cytarabine over three cycles, developed febrile neutropenia requiring amikacin, and was subsequently started on imatinib 400 mg in view of the BCR-ABL1 positivity. What makes this case worth reporting is the convergence of three issues that each present their own challenges: establishing a diagnosis of de novo AML rather than CML in blast crisis, managing an already aggressive disease made more so by a complex karyotype, and deciding on the role of tyrosine kinase inhibitors in a disease setting where their use is not yet standardized. Detailed cytogenetic workup proved critical in navigating all three.

After the first TFR attempt, major molecular response (MMR) was lost, and ponatinib was initiated but discontinued because of cerebral infarction. Imatinib was reintroduced, leading to the reachievement of a deep molecular response. This case underscores the importance of careful patient selection and long-term molecular monitoring following TFR attempts, including those involving novel TKIs such as asciminib.

Clinically available SFK inhibitors, particularly dasatinib, synergistically enhance ATRA-induced myeloid differentiation of NB4 APL cells and are more effective than the conventional ATRA plus ATO combination in this in vitro model. These findings support further preclinical and clinical evaluation of SFK inhibitor plus ATRA combinations as differentiation-oriented strategies and potential alternatives or complements to ATO-containing regimens in APL.

We report an octogenarian man with chronic-phase CML who was intolerant to multiple tyrosine kinase inhibitors and underwent temporary discontinuation of asciminib. All-trans retinoic acid plus arsenic trioxide achieved molecular remission of PML::RARA and was followed by an initial marked reduction in BCR::ABL1 transcript levels, which subsequently remained detectable at low levels during continued follow-up. This case highlights the importance of integrated cytogenetic and molecular evaluation to distinguish blast phase from independent leukemogenesis in patients with CML who develop cytopenias.

The landscape of asciminib resistance is broader and more complex than previously appreciated, involving mutations across multiple domains that disrupt ABL1 autoinhibition. Epistasis between mutations acquired during sequential therapies can create unexpected and potent resistance. However, these diverse genetic resistance mechanisms converge on a single biophysical measurement of the openness of the active ABL1 conformation. This provides a unified framework for understanding asciminib resistance and underscores the need for routine clinical resistance monitoring to include the SH3 and SH2 domains in first line and later line therapy.

We describe a case of complete and durable remission achieved with imatinib monotherapy in an unresectable mesenteric desmoid tumour with the patient remaining disease-free at 10 years. This case highlights the potential for long-term complete response and underscores the need for prospective data to guide treatment duration and cessation criteria.

Among the synthesized molecules, F-4 demonstrated the strongest activity against K562 cells with an IC50 value of 6.85 µM, close to that observed for imatinib (IC50 = 5.20 µM)... The findings identify F-4 as a promising new thiazolone-derived scaffold with selective anti-CML activity and notable ABL TK inhibitory potential. Additional structural optimization may further enhance its binding characteristics and therapeutic efficacy.

The introduction of imatinib established proof of principle for oncogene-targeted therapy, leading to sustained survival improvements...More recently, the development of the allosteric inhibitor asciminib introduced a novel mechanism of action and expanded therapeutic options for pretreated patients...Thus, CML represents a unique model of translational oncology, demonstrating how mechanistic insight can drive therapeutic innovation. Future strategies will focus on increasing TFR rates, overcoming resistance, targeting leukemic stem cells, and improving global access to therapy and monitoring, with the ultimate aim of achieving functional cure in the majority of patients.

Ferrocene-based analogues can sustain stable ABL1 binding via non-classical interaction networks independent of hinge recognition. The clear distinction between active compounds and the inactive analogue 15e supports the robustness of the proposed binding mode and provides a structural basis for their reported cytotoxic activity. These findings support further experimental evaluation of ferrocene-containing scaffolds as potential BCR-ABL1 inhibitors.