ABL1 (ABL proto-oncogene 1)

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.

The patient received therapeutic anticoagulation, low-dose aspirin, and hydroxyurea. This case highlights the role of multimodal imaging in diagnosis and risk stratification, and the need to consider masked polycythemia vera in unprovoked pulmonary embolism with unexplained microcytosis and elevated red blood cell count.

We identified FDA-approved compounds acting through these pathways, three of which, Ribociclib, Ponatinib, and Dasatinib, showed superior efficacy to current therapies across renal cancer cell lines in preclinical screens. By acting through mechanisms distinct from current therapies, they represent promising candidates for combination strategies aimed at overcoming resistance and improving clinical outcomes in ccRCC.

This specific clone persisted after discontinuation, suggesting a role in the sustained immune surveillance of residual leukemia stem cells. These findings suggest that the quality of immune reconstitution, specifically the induction of innate-like effector T-cell clones, may be a more critical determinant of TFR success than the absolute duration of therapy.

P1, N=30, Recruiting, OHSU Knight Cancer Institute | Trial completion date: May 2026 --> May 2028 | Trial primary completion date: Mar 2026 --> Mar 2027

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.

The patient was treated with cladribine (40 mg over five days) followed by maintenance hydroxyurea (300 mg twice daily), with significant clinical improvement at eight-week follow-up. This case underscores that SM-AHN can present with isolated hepatosplenomegaly and profound leukocytosis without cutaneous signs, and highlights the critical role of integrated molecular profiling, including KIT mutation analysis, in the diagnostic workup of atypical hematologic presentations.

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.

Three cases (8%) of non-fatal sinusoidal obstructive syndrome (SOS) were observed. Inotuzumab was safe and effective at eradicating MRD.

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.