A novel role of BMP4 in adult hematopoietic stem and progenitor cell homing via Smad independent regulation of integrin-α4 expression

Although it is well established that BMP4 plays an important role in the development of hematopoietic system, it is less well understood whether BMP4 affects adult hematopoiesis and how. Here, we describe a novel mechanism by which BMP4 regulates homing of murine as well as human hematopoietic stem/progenitor cells (HSPCs). BMP4 treatment of murine BM derived c-kitLin-Sca-1 (KLS) and CD150CD48-KLS cells for up to 5 days in vitro prevented the culture-induced loss of Integrin-α4 (ITGA4) expression as well as homing. The effect on ITGA4 expression in response to BMP4 is mediated via SMAD-independent phosphorylation of p38 MAPK, which activates microphthalmia-associated transcription factor (MITF), known to induce ITGA4 expression. Elevated ITGA4 expression significantly enhanced HSPC attachment to bone marrow stromal cells, homing and long-term engraftment of the BMP4 treated cells compared with the cells cultured without BMP4. BMP4 also induced expression of ITGA4 on human BM derived Lin-CD34 cells in culture, which was associated with improved homing potential. Thus, BMP4 prevents culture-induced loss of ITGA4 expression on HSPCs in a SMAD-independent manner, resulting in improved homing of cultured HSPCs and subsequent hematopoietic reconstitution.

CLL clonal heterogeneity: an ecology of competing subpopulations

In this issue of Blood , Schuh et al report the detection of heterogeneous patterns of clonal evolution in 3 patients with IgHV unmutated CLL over the lifetime of their disease using whole-genome sequencing (WGS).[1][1]One of the clinical hallmarks of chronic lymphocytic leukemia (CLL) is the high

Role of Gas6 in Cancer-Induced Venous Thrombosis

Residence Proximity to Benzene Release Sites Is Associated with Increased Incidence of Non-Hodgkin Lymphoma.

JAK2 V617F Genotype Is a Strong Determinant of Blast Transformation in Primary Myelofibrosis.

Impact of Pretransplant Donor and Recipient Cytomegalovirus Serostatus On Outcome for Multiple Myeloma Patients Undergoing Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

The Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia

Pulmonary hypertension in COPD: results from the ASPIRE registry

The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naïve cases of pulmonary hypertension in COPD. Mean ± SD follow-up was 2.3 ± 1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild-moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival. Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.

Coronary risk assessment among intermediate risk patients using a clinical and biomarker based algorithm developed and validated in two population cohorts

Many coronary heart disease (CHD) events occur in individuals classified as intermediate risk by commonly used assessment tools. Over half the individuals presenting with a severe cardiac event, such as myocardial infarction (MI), have at most one risk factor as included in the widely used Framingham risk assessment. Individuals classified as intermediate risk, who are actually at high risk, may not receive guideline recommended treatments. A clinically useful method for accurately predicting 5-year CHD risk among intermediate risk patients remains an unmet medical need.

Main characteristics and participation rate of European adolescents included in the HELENA study

Background Participation rate and response rate are key issues in a cross sectional large-scale epidemiological study. The objective of this paper is to describe the study population and to evaluate participation and response rate as well as the key nutritional status variables in male and female adolescents involved in the HELENA study. Methods A multi-stage random cluster sampling with a target sample of 3000 adolescents aged [12.5 to 17.5] years, stratified for geographical location and age, was carried out. Information for participants and non-participants (NP) was compared, and participation and response rates to specific questionnaires were discussed. Results 3,865 adolescents aged [12.5 to 17.5] years (1,845 females) participated in the HELENA study, of whom 1,076 (568 females) participated in the blood sampling. 3,528 (1,845 females) adolescents were finally kept for statistical analysis. Participation rates for the schools and classes differed importantly between countries. The participation rate of pupils within the participating classes also differed importantly between countries. Sex ratio, mean age and BMI were similar between NP and participating adolescents within each centre, and in the overall sample. For all the questionnaires included in the database, the response rate of questionnaires was high (more than 80% of questions were completed). Conclusion From this study it could be concluded that participation rate differed importantly between countries, though no bias could be identified when comparing the key study variables between participants and non-participants. Response rate for questionnaires was very high. Future studies investigating lifestyle and health in adolescents can optimize their methods when considering the opportunities and barriers observed in the HELENA study.