ABL1 (ABL proto-oncogene 1)

Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Evolution in defining risk through clinical and molecular characterization should increase ability to identify emerging advanced disease, minimize progression and improve treatment of resistant chronic phase and blast phase disease. While BCR::ABL1 tyrosine kinase inhibition remains central in advanced disease, combination therapy with conventional and novel chemotherapy, immunotherapy, and allogeneic stem cell transplantation provide best long-term outcomes.

Furthermore, simulated therapies targeting the stem cell-like compartment indicate that blocking transitions to the CD34+/CD38- state (i.e. blocking dedifferentiation) is more effective than promoting transitions from the CD34+/CD38- state toward other states (i.e. promoting differentiation) to reduce the proportion of CD34+/CD38- cells. The modeling framework used here is a novel, useful tool to infer prognosis and genotype from routine flow cytometry.

We found increased DNA-damage in HSPCs from these mice, including a BCR::ABL1 kinase-domain mutation found in TKI-resistant human CML. These studies suggest long Oxr1 detoxifies ROS to decrease mutagenesis in CML, but aberrant short Oxr1 expression enhances progression.

Maslinic acid (MA), a plant-derived pentacyclic triterpene, was compared to the FDA-approved drugs dasatinib (DAS) and doxorubicin (DOX) to determine its antileukemic potential. Thus, these results illustrate that MA may act as a natural scaffold with antileukemic properties and call for additional experimental confirmation. The online version contains supplementary material available at 10.1007/s40203-025-00478-3.

Together, these findings reveal a novel mechanism where Riluzole promotes apoptosis through upregulation of EGR1 , which then cooperates with YAP/p73 to activate Bax expression. These insights establish Riluzole as a promising therapeutic intervention for OS treatment through modulation of the EGR1 /Yap/p73/Bax signaling axis.

CD26+LSCs were elevated in patients in treatment-free remission (TFR), while EVES BCR::ABL1 levels were higher in those receiving therapy. These findings suggest distinct dynamics between LSC populations and vesicle-mediated transcript release, with potential implications for CML monitoring and prognosis.

The analysis of clinical database revealed that elevated U2SURP in HSCs was correlated with the occurrence of CML. In conclusion, our data suggested that targeting circ_0058493/miR-548b-3p/U2SURP axis and exosomal circ_0058493 is a potential therapeutic strategy for improving imatinib efficacy in CML.

P2, N=42, Recruiting, Sheng-Li Xue, MD | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2025 --> Oct 2026

P3, N=406, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2031 --> Jan 2028

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2025 --> Nov 2026