BCR (BCR Activator Of RhoGEF And GTPase)

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.

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.

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 have collected both computational studies and experimental reports, including functional assays, mechanistic studies of inhibition, and structural approaches that have evaluated PKIs' effects on ABC transporters. We conclude that although PKIs can be ABC substrates, they mainly inhibit drug efflux, with minimal and context-dependent effects on transporter expression or localization.

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.

P1, N=60, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Aug 2026 --> May 2026

P=N/A, N=10, Active, not recruiting, University College, London | Recruiting --> Active, not recruiting

CD26 + LSCs can be a useful marker in follow up of patients with CML. Despite promising findings, the limited sample size highlight the need for larger, prospective studies to validate these results and assess the predictive value of CD26 + LSCs for TKI discontinuation strategies.

The patient was treated with cytoreductive therapy, followed by imatinib, with a favorable clinical and hematologic response. This case highlights the potential for massive splenomegaly to mask CML and emphasizes the importance of early molecular testing. Splenectomy may unmask underlying hematologic malignancy through significant postoperative hematologic changes.

P2, N=131, Completed, Versailles Hospital | Active, not recruiting --> Completed

Moreover, N-acetylcysteine inhibited CCCP-induced reactive oxygen species production, prevented mitochondrial translocation of p210 BCR-ABL, and fully restored ERK-activation. These findings suggest that intercellular relocation of p210 BCR-ABL dynamically rewires downstream signaling networks, potentially optimizing the signaling balance required for CML cell survival and proliferation.

Vodobatinib demonstrates a favorable preclinical absorption, distribution, metabolism, and excretion profile, with high metabolic stability, minimal efflux liability, and selective tissue distribution. These findings support its continued clinical development in chronic myeloid leukemia and potentially other Bcr-Abl 1 driven malignancies.