A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis.

The age-associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy.

HMA/VEN treatment modifications and associated outcomes in -mutant AML.

Hypomethylating agents (HMA) and venetoclax (VEN) are commonly used in patients with -mutated (m) acute myeloid leukemia (AML) ineligible for induction chemotherapy. While prior studies demonstrated high response and survival rates with HMA/VEN in m AML, the impact of treatment modifications in real-world settings is unclear. We retrospectively reviewed 89 m AML patients treated with HMA/VEN from January 2018 to June 2023.

Phase 1 study of JNJ-64619178, a protein arginine methyltransferase 5 inhibitor, in patients with lower-risk myelodysplastic syndromes.

Splicing factor (SF) gene mutations are frequent in myelodysplastic syndromes (MDS), and agents that modulate RNA splicing are hypothesized to provide clinical benefit. JNJ-64619178, a protein arginine methyltransferase 5 (PRMT5) inhibitor, was evaluated in patients with lower-risk (LR) MDS in a multi-part, Phase 1, multicenter study. The objectives were to determine a tolerable dose and to characterize safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity.

Repurposing Immunomodulatory Therapies against Coronavirus Disease 2019 (COVID-19) in the Era of Cardiac Vigilance: A Systematic Review.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance.

The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent.

Background: Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting.

Patients And Methods: We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI.

Self-Incompatibility Triggers Irreversible Oxidative Modification of Proteins in Incompatible Pollen.

Self-incompatibility (SI) is used by many angiosperms to prevent self-fertilization and inbreeding. In common poppy (), interaction of cognate pollen and pistil -determinants triggers programmed cell death (PCD) of incompatible pollen. We previously identified that reactive oxygen species (ROS) signal to SI-PCD.

PI3 kinase alpha and delta promote hematopoietic stem cell activation.

Many cytokines and chemokines that are important for hematopoiesis activate the PI3K signaling pathway. Because this pathway is frequently mutated and activated in cancer, PI3K inhibitors have been developed for the treatment of several malignancies, and are now being tested in the clinic in combination with chemotherapy. However, the role of PI3K in adult hematopoietic stem cells (HSCs), particularly during hematopoietic stress, is still unclear.

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.

Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation.

Identification of Phosphorylation Sites Altering Pollen Soluble Inorganic Pyrophosphatase Activity.

Protein phosphorylation regulates numerous cellular processes. Identifying the substrates and protein kinases involved is vital to understand how these important posttranslational modifications modulate biological function in eukaryotic cells. Pyrophosphatases catalyze the hydrolysis of inorganic phosphate (PP) to inorganic phosphate P, driving biosynthetic reactions; they are essential for low cytosolic inorganic phosphate.

Self-incompatibility-induced programmed cell death in field poppy pollen involves dramatic acidification of the incompatible pollen tube cytosol.

Self-incompatibility (SI) is an important genetically controlled mechanism to prevent inbreeding in higher plants. SI involves highly specific interactions during pollination, resulting in the rejection of incompatible (self) pollen. Programmed cell death (PCD) is an important mechanism for destroying cells in a precisely regulated manner.

Self-incompatibility in Papaver: advances in integrating the signalling network.

Self-fertilization, which results in reduced fitness of offspring, is a common problem in hermaphrodite angiosperms. To prevent this, many plants utilize SI (self-incompatibility), which is determined by the multi-allelic S-locus, that allows discrimination between self (incompatible) and non-self (compatible) pollen by the pistil. In poppy (Papaver rhoeas), the pistil S-determinant (PrsS) is a small secreted protein which interacts with the pollen S-determinant PrpS, a ~20 kDa novel transmembrane protein.