Clofarabine Has a Superior Therapeutic Window as compared to Gemcitabine in Preclinical Bladder Cancer Models.

Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses.

Kinase-inactivated CDK6 preserves the long-term functionality of adult hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin-dependent kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. Herein, we describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal, and differentiation in activated HSCs.

Recent contributions of single-cell and spatial profiling to the understanding of bladder cancer.

Purpose Of Review: Current risk stratification and treatment decision-making for bladder cancer informed by histopathology as well as molecular diagnostics face limitations. This review summarizes recent advancements in single-cell and spatial omics methodologies for understanding bladder cancer biology and their potential impact on development of novel therapeutic strategies.

Recent Findings: Single-cell RNA sequencing and spatial omics techniques offer unprecedented insights into various aspects of tumor microenvironment (TME), bladder cancer heterogeneity, cancer stemness, and cellular plasticity.

A lineage-specific STAT5BN642H mouse model to study NK-cell leukemia.

Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia, although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice.

SBNO2 is a critical mediator of STAT3-driven hematological malignancies.

Gain-of-function mutations in the signal transducer and activator of transcription 3 (STAT3) gene are recurrently identified in patients with large granular lymphocytic leukemia (LGLL) and in some cases of natural killer (NK)/T-cell and adult T-cell leukemia/lymphoma. To understand the consequences and molecular mechanisms contributing to disease development and oncogenic transformation, we developed murine hematopoietic stem and progenitor cell models that express mutated STAT3Y640F. These cells show accelerated proliferation and enhanced self-renewal potential.