BCR (BCR Activator Of RhoGEF And GTPase)

The cells still exhibited high lineage plasticity, switching from a myeloid to a B-lymphoid identity in vivo. In conclusion, this model enables the mechanistic dissection of MLL fusion variants in vitro and in vivo, providing a foundation for developing targeted therapies for MLL-rearranged leukemias.

P1/2, N=26, Not yet recruiting, Memorial Sloan Kettering Cancer Center | Phase classification: P2 --> P1/2 | Initiation date: Mar 2026 --> Jun 2026

Overall, this work applies bioisosteric replacement to generate a new chemotype and uncovers a mechanistically divergent lead. The distinct, ABL1-independent mechanism of compound 2a establishes a solid foundation for future optimization and highlights its potential as a starting point for developing novel antimyeloproliferative agents with a different therapeutic profile.

Additionally, we critically assess the therapeutic potential of targeting this switch, emphasizing how drugs that either inhibit or promote autophagy can work together with arsenic trioxide (ATO) to combat drug resistance in solid tumors such as glioblastoma and ovarian cancer. By shifting from simple descriptions to a detailed mechanistic and contextual understanding, this review offers a valuable guide for future research aiming to harness the autophagy switch for cancer prevention and personalized treatment.

Our experimental studies provide evidence that Ku80-Ct and 28-mer peptide Ku3 reduce MLLbcr breakage after doxorubicin treatment independently of DNA-PK activity. Proximity ligation and single molecule tracking studies show that Ku3 antagonizes Ku80-EndoG association and modulates chromatin-binding of EndoG. Such MLLbcr protection blocks EndoG´s pro-tumorigenic functions without limiting cytotoxicity, pursued for co-treatments that reduce secondary leukemia, a severe side effect of chemotherapy.

Leveraging cellular selectivity and engineered stability, CRUSH offers a mixed-and-read diagnostic test, where lyophilized sensors are directly mixed with whole blood samples, followed by standard flow cytometry analysis. This one-step test detects BCR-ABL1 fusions in living myeloid cells with high specificity and robustness, enabling accurate discrimination of multilineage acute lymphoblastic leukemia within 1 h. Our study bridges biosensing innovation with urgent diagnostic needs, offering a rapid, specific, and robust tool for accurate diagnosis and treatment of hematologic malignancies.

Human patient gene expression data suggested that the levels of sympathetic nerve receptor expression change during the blastic transformation of human CML. Our findings indicate that the sympathetic nervous system regulates the pathogenesis of myeloid leukemia and could play a crucial role in the disease progression of myeloid leukemia.

The genetic changes included GOF mutations (KRAS, BRAF genes, etc.), LOF mutations (STAG1, SMARCA2 genes, etc.), gene fusions (BCR-ABL1, PAX3-FOXO1, etc.), and amplification (CPM, BEST3, etc.). Therefore, many different molecular mechanisms act as predictors of tumor cell response to inhibition of supertarget genes.

Both imatinib and nilotinib therapies lead to significant increases in BP, with nilotinib showing a greater hypertensive effect. Monitoring BP is crucial, especially for patients on second-generation TKIs, to manage cardiovascular risks associated with long-term treatment.

An experimental evaluation over curated UniProtKB sets of CML-associated proteins indicates improved performance, with an accuracy of 97.5% and a 0.98 ROC-AUC. The proposed framework delivers breakthroughs to computational oncology and enables early, non-invasive screening for CML.

Furthermore, ponatinib increases chimeric antigen receptor (CAR) TSCM cells by reducing CAR T cell exhaustion, resulting in durable antitumor efficacy. Our results thus implicate ponatinib as therapeutic immunomodulator, inducing TSCM cells for improved antitumor T cell activity.

Dasatinib de-escalation after 100 mg standard dose achieved superior early response, fewer discontinuations, and sustained outcomes versus upfront low-dose therapy. This first Indian study supports de-escalation as an effective, real-world dose-optimization strategy.