Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome is a distinct form of leukemia or preleukemia that mirrors the hematological features of acute megakaryoblastic leukemia. However, it typically resolves spontaneously in the early stages. TAM originates from fetal liver (FL) hematopoietic precursor cells and emerges due to somatic mutations in GATA1 in utero. In TAM, progenitor cells proliferate and differentiate into mature megakaryocytes and granulocytes. This process occurs both in vitro, aided by hematopoietic growth factors (HGFs) produced in the FL, and in vivo, particularly in specific anatomical sites like the FL and blood vessels. The FL\'s hematopoietic microenvironment plays a crucial role in TAM\'s pathogenesis and may contribute to its spontaneous regression. This review presents an overview of current knowledge regarding the unique features of TAM in relation to the FL hematopoietic microenvironment, focusing on the functions of HGFs and the pathological features of TAM.

The incidence of cardiovascular diseases increases with age and is also correlated with increased inflammatory burden. Recently, human genetics provided a new paradigm linking aging, inflammation, and atherosclerotic cardiovascular disease (ASCVD). Next-generation genetic sequencing of whole blood-derived DNA in humans showed that clonal expansion of hematopoietic cells with somatic mutations in leukemogenic genes was associated with age and correlated with increased mortality. This phenomenon, termed clonal hematopoiesis of indeterminate potential (CHIP), was associated with hematologic malignancy as well as ASCVD independently of age and other traditional risk factors. Because the implication of CHIP with ASCVD, genetic loss-of-function studies of Tet2 and Dnmt3a in murine models have supported a mechanistic role for CHIP in promoting vascular disease. Despite the potential contribution of CHIP to myriad cardiovascular and aging-related diseases, the epidemiology and biology surrounding this phenomenon remains incompletely appreciated and understood, especially as applied to clinical practice and prognostication. Here, the authors review this emerging key risk factor, defining its discovery, relationship to cardiovascular diseases, preclinical evidence for causality, and implications for risk prediction and mitigation.

OBJECTIVE: Clozapine is the favoured antipsychotic for treatment-refractory schizophrenia, but has a 1%-2% incidence of agranulocytosis. Patients who require chemotherapy therefore pose a unique management dilemma for haematologists, oncologists and psychiatrists.
METHODS: The Ovid MEDLINE and EMBASE databases were searched to identify reports describing use of clozapine concurrent with chemotherapy until 31 March 2019. The following terms (with variations) were used: neoplasm, cancer, tumour, malignancy, chemotherapy, antineoplastic and clozapine.
RESULTS: Twenty-seven cases were included after reviewing titles and abstracts for relevance. Fifteen patients had solid organ tumours, and 12 had haematological malignancies, including three who underwent autologous haematopoietic stem cell transplantation (AutoHSCT). Clozapine was continued in 14 cases (albeit dose reduced in 2), with a reported median neutropaenic nadir of 0.29 × 109 /L (range 2.2 to <0.0 × 109 /L). Clozapine was discontinued or substituted for another antipsychotic in the remaining 13 cases, all except one of whom experienced marked psychiatric deterioration. The only neutropenia-related complication was one case of bacteraemia with high-dose melphalan conditioning for AutoHSCT.
CONCLUSIONS: These findings argue in favour of clozapine continuation during chemotherapy. Further research is needed to develop guidance to minimise the risk of neutropenia-related complications from concurrent treatment.

The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts the feedback to positive control. Based on these relationships, agents inhibiting cyclo-oxygenases, known as non-steroidal anti-inflammatory drugs (NSAIDs), can activate hematopoiesis and be protective or curative under myelosuppressive states. The effectiveness of therapeutic use of NSAIDs in these situations is expressive especially under the selective inhibition of cyclooxygenase-2 (COX-2), when undesirable side effects of cyclooxygenase-1 inhibition, like gastrointestinal damage, are absent. The effects of the clinically approved selective COX-2 inhibitor, meloxicam, were investigated and demonstrated significant hematopoiesis-stimulating and survival-enhancing actions of this drug in sublethally or lethally γ-irradiated mice. These effects were connected with the ability of meloxicam to increase serum levels of the granulocyte colony-stimulating factor. It can be inferred from these findings that selective COX-2 inhibitors might find their use in the treatment of myelosuppressions of various etiologies.