BCR-ABL1 mutation

P2, N=14, Terminated, Gruppo Italiano Malattie EMatologiche dell'Adulto | Active, not recruiting --> Terminated; low enrollment rate

P1/2, N=11, Terminated, Takeda | Completed --> Terminated; Phase 1 enrollment was terminated due to dose-limiting toxicities, thus the study was terminated by Sponsor.

P2, N=283, Active, not recruiting, Takeda | Trial completion date: Dec 2024 --> Mar 2025

A linear relationship was found between reported and assigned values for all levels of the reference standards when tested across 3 different BCR-ABL RT-qPCR assays, enabling the calculation of an assay-specific CF to allow harmonized reporting on the International Scale (%IS). The BCR-ABL p210 Panel was validated for accuracy, precision, robustness, and traceability, and can be used as a WHO traceable reference standard to create assay-specific CF to enable standardized reporting on the International Scale (%IS).

Because of the above, further research is needed to explore whether using upfront immunotherapy like inotuzumab ozogamicin or blinatumomab in the upfront setting, as well as administering allogeneic transplant early in the treatment course of muTP53-ALL would decrease the risk of relapse and improve long-term survival. Although muTP53 ALL achieved a higher MRD-FC negative response compared to wtTP53 ALL, this did not translate into long-term survival in the muTP53 ALL. Whether using NGS for B-cell and T-cell receptors as a method for MRD testing, like clonoSEQ®, would provide a better prognostic tool is currently unknown.

P3, N=173, Recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: Apr 2025 --> Dec 2027 | Trial primary completion date: Jan 2025 --> Jun 2026

The primary treatment for chronic myeloid leukemia (CML) involves first- and second-generation tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, bosutinib, and dasatinib. It includes in silico calculations, such as the octanol/water partition coefficient (cLogP) via SwissAdme, and 2D maps of intermolecular interactions through molecular docking. This approach enhances understanding for both specialists and those interested in medicinal chemistry and pharmacology, while also contextualizing future directions for further optimizations of ponatinib, facilitating the development of new analogs of this crucial inhibitor for the treatment of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

The RM was used to evaluate inter-laboratory reproducibility in eight different laboratories, demonstrating that participating laboratories could consistently produce copy concentrations of b3a2 and ABL1-ref, as well as the BCR-ABL1/ABL1 ratio (CV < 2.0%). This work suggests that the RM can be employed in establishing metrological traceability for detecting mutations in the BCR-ABL1 fusion gene, as well as in quality control for testing laboratories.

Ocular findings related to CML are rare, with the lowest incidence when compared to other leukemias, and are associated with worse outcomes. Posterior segment findings include intraretinal hemorrhages, Roth spots, and retinal infiltrates. This unique case describes an RRD in CML retinopathy with an aggressive course and poor anatomical result.

P1/2, N=68, Active, not recruiting, Takeda | Trial completion date: Aug 2027 --> Jan 2027 | Recruiting --> Active, not recruiting

Intriguingly, when the son developed MPAL, the mother did not develop donor-derived leukemia and remained in remission. Our cases provide valuable insights to guide future research on familial MPAL.

The frequency of cancer driver mutations among tissues is non-uniform: for instance, mutations in APC are particularly frequent in colorectal cancer, and 99% of chronic myeloid leukemia patients harbor the driver BCR-ABL1 fusion mutation, which is rarely found in solid tumors. Here, we provide a mechanistic framework that aims to explain how tissue-specific features, ranging from epigenetic underpinnings to the expression of viral transposable elements, establish a molecular basis for selecting cancer driver mutations in a tissue-specific manner.