ABL1 (ABL proto-oncogene 1)

P1, N=20, Recruiting, The First Affiliated Hospital of Soochow University | Active, not recruiting --> Recruiting | Trial primary completion date: Jul 2026 --> Nov 2025

P1, N=24, Recruiting, Mendus

Imatinib 400 mg daily was initiated but was replaced with dasatinib 100 mg daily because of intolerance. This case highlights the diagnostic complexity of synchronous hematologic malignancies and the importance of comprehensive multimodal evaluation when clinical, morphologic, and laboratory findings are not fully explained by a single diagnosis. Treating the clinically dominant clone while monitoring the second clone may be appropriate when the latter is asymptomatic.

The observed common spatial distribution of fNBP1 and BCR-ABL enhances the understanding of this protein complex's formation, suggesting a potential role for fNBP1 in CML development.

At present, however, this evidence base is constrained by small and heterogeneous cohorts, limited cross-platform reproducibility, and a scarcity of independent external validation for candidate protein panels. Realising this vision will require multicentre standardisation, analytically validated panel assays, and prospective clinical studies that translate molecular findings into decision-grade tools for patients with MPNs.

This case highlights the limitations of isolated diagnostic modalities in early hematologic malignancy and underscores the importance of integrating clinical, laboratory, morphologic, immunophenotypic, and imaging findings. Persistent clinical suspicion should prompt timely tissue-based evaluation despite initially inconclusive studies to avoid delays in definitive diagnosis and management.

CML and PV exhibited distinct cytokine-driven transcriptional signatures, whereas ET and PMF exhibited minimal alterations. These findings support the clinical utility of NanoString technology for bone marrow specimens and highlight disease-specific immune pathways as potential diagnostic biomarkers in MPNs.

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

P2, N=40, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: May 2026 --> Nov 2026

P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

Among patients with chronic myeloid leukemia (CML) aiming for tyrosine kinase inhibitor (TKI) discontinuation, second-generation TKIs (2G-TKIs) are used as one of the first-line options because they induce faster and deeper molecular responses than imatinib...We analyzed 431 patients enrolled in the phase III Japan Adult Leukemia Study Group (JALSG) CML212 trial, comparing nilotinib at 300 mg twice daily (n = 218) and dasatinib at 100 mg once daily (n = 213) as first-line therapy...In multivariable models, HT(0-3) (subdistribution hazard ratio [HR], 2.23; 95% CI, 1.09-4.55) and the 6-month IS (HR, 0.38; 95% CI, 0.31-0.47) were independent predictors of MR4.5 attainment, whereas only the 6-month IS predicted TDE (odds ratio, 0.37; 95% CI, 0.24-0.56). This study demonstrates that molecular response at 6 months after TKI initiation has important clinical value in early stratification of MR4.5 attainment and TDE in patients receiving 2G-TKI therapy.

Furthermore, LO metabolically reprogram MSC and prime MSC towards differentiation into adipocytes capable of sustaining B-ALL cell growth. Thus, LO-educated MSC, and the adipocytes derived from them, support B-ALL cells by distinct mechanisms, and targeting of LO-mediated communication pathways to prevent B-ALL progression has potential for the development of novel adjuvant treatment strategies.