Understanding the Role of Activation Loop Mutants in Drug Efficacy for FLT3-ITD.

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants.

PLK1 as a cooperating partner for BCL2-mediated antiapoptotic program in leukemia.

The deregulation of BCL2 family proteins plays a crucial role in leukemia development. Therefore, pharmacological inhibition of this family of proteins is becoming a prevalent treatment method. However, due to the emergence of primary and acquired resistance, efficacy is compromised in clinical or preclinical settings.

Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling.

Therapy resistance remains one of the major challenges for cancer treatment that largely limits treatment benefits and patient survival. The underlying mechanisms that lead to therapy resistance are highly complicated because of the specificity to the cancer subtype and therapy. The expression of the anti-apoptotic protein BCL2 has been shown to be deregulated in T-cell acute lymphoblastic leukemia (T-ALL), where different T-ALL cells display a differential response to the BCL2-specific inhibitor venetoclax.

A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.

Despite incredible progress in cancer treatment, therapy resistance remains the leading limiting factor for long-term survival. During drug treatment, several genes are transcriptionally upregulated to mediate drug tolerance. Using highly variable genes and pharmacogenomic data for acute myeloid leukemia (AML), we developed a drug sensitivity prediction model for the receptor tyrosine kinase inhibitor sorafenib and achieved more than 80% prediction accuracy.