Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL.

Malignant transformation of T-cell progenitors causes T-cell acute lymphoblastic leukemia (T-ALL), an aggressive childhood lymphoproliferative disorder. Activating mutations of Notch, Notch1 and Notch3, have been detected in T-ALL patients. In this study, we aimed to deeply characterize hyperactive Notch3-related pathways involved in T-cell dynamics within the thymus and bone marrow to propose these processes as an important step in facilitating the progression of T-ALL.

Thymic-Epithelial-Cell-Dependent Microenvironment Influences Proliferation and Apoptosis of Leukemic Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological cancer characterized by the infiltration of immature T-cells in the bone marrow. Aberrant NOTCH signaling in T-ALL is mainly triggered by activating mutations of NOTCH1 and overexpression of NOTCH3, and rarely is it linked to NOTCH3-activating mutations. Besides the known critical role of NOTCH, the nature of intrathymic microenvironment-dependent mechanisms able to render immature thymocytes, presumably pre-leukemic cells, capable of escaping thymus retention and infiltrating the bone marrow is still unclear.

Effect of Protein Corona on the Drug Delivery of Carbogenic Nanodots and Their Mapping by Fluorescence Lifetime Imaging Microscopy.

It is practically impossible to avoid the nonspecific binding of protein to a nanocarrier when it enters a biological fluid. This hinders the chemotherapeutic efficacy of the nanocarrier to a large extent. Surface functionalization, in the recent past, helped in reducing such nonspecific interactions.

When Viruses Cross Developmental Pathways.

Aberrant regulation of developmental pathways plays a key role in tumorigenesis. Tumor cells differ from normal cells in their sustained proliferation, replicative immortality, resistance to cell death and growth inhibition, angiogenesis, and metastatic behavior. Often they acquire these features as a consequence of dysregulated Hedgehog, Notch, or WNT signaling pathways.

Quercetin acts as a P-gp modulator via impeding signal transduction from nucleotide-binding domain to transmembrane domain.

The inherent ability of the cancer cells to resist chemotherapeutic agents is a major challenge in drug discovery. Chemotherapy is one of the most widely used treatment methods for cancer, but due to multidrug resistance (MDR) development in cancer cells, the healing procedure often fails. Various factors impart cancer resistance to cells; among them, P-glycoprotein (P-gp) overexpression is directly linked to MDR in cancer cells.