EGFR-mutation testing, treatment patterns and clinical outcomes in patients with stage IB-IIIA non-small cell lung cancer in Norway-a nationwide cohort study.

Introduction: Testing for mutations of epidermal growth factor receptor (EGFR) is crucial to identify non-small cell lung cancer (NSCLC) patients eligible for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs); This study aims to describe EGFR-mutation testing, treatment patterns, and overall survival (OS) in localized NSCLC patients.

Materials And Methods: Patients with localized (Stage IB-IIIA) NSCLC registered in the Norwegian Cancer Registry during 2010-2017 were followed from diagnosis until emigration, death, or end of study in 2018. The cohort was linked to data from the Norwegian Patient Registry, the Prescription Database, and the Cause of Death Registry.

Improved overall survival for Stage III NSCLC patients treated with curative-intended therapy from 2010 to 2018-a cohort study in Denmark.

Background: Despite advances in treatment strategies and improved clinical outcomes, an unmet need remains for NSCLC patients. With an increased real-world knowledge of NSCLC, clinicians could offer patients optimal tailored treatment and disease management. In this retrospective cohort study, we describe patient characteristics, treatment patterns and modality, and survival in NSCLC patients diagnosed and treated at Aarhus University Hospital, Denmark.

Infections in patients with multiple sclerosis: A national cohort study in Sweden.

Background: Multiple sclerosis (MS) patients have an increased risk of infections, but few population-based studies have reported infections occurring in MS in the years immediately after diagnosis.

Objective: To explore incident infections in MS, stratified by age and sex.

Methods: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years), matched at diagnosis with 61,828 matched MS-free individuals were identified between 1st January 2008 and 31st December 2016, using national registers.

A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes.

Established cell culture systems have failed to accurately recapitulate key features of terminal erythroid maturation, hampering our ability to in vitro model and treat diseases with impaired erythropoiesis such as myelodysplastic syndromes with ring sideroblasts (MDS-RS). We developed an efficient and robust three-dimensional (3D) scaffold culture model supporting terminal erythroid differentiation from both mononuclear (MNC) or CD34-enriched primary bone marrow cells from healthy donors and MDS-RS patients. While CD34 cells did not proliferate beyond two weeks in 2D suspension cultures, the 3D scaffolds supported CD34 and MNC erythroid proliferation over four weeks demonstrating the importance of the 3D environment.

-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells.

Mutations in the RNA splicing gene are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in in 39 of 40 cases (97.

Aberrant splicing of genes involved in haemoglobin synthesis and impaired terminal erythroid maturation in SF3B1 mutated refractory anaemia with ring sideroblasts.

Refractory anaemia with ring sideroblasts (RARS) is distinguished by hyperplastic inefficient erythropoiesis, aberrant mitochondrial ferritin accumulation and anaemia. Heterozygous mutations in the spliceosome gene SF3B1 are found in a majority of RARS cases. To explore the link between SF3B1 mutations and anaemia, we studied mutated RARS CD34(+) marrow cells with regard to transcriptome sequencing, splice patterns and mutational allele burden during erythroid differentiation.

SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts.

Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions.

The transporter ABCB7 is a mediator of the phenotype of acquired refractory anemia with ring sideroblasts.

Refractory anemia with ring sideroblasts (RARS) is characterized by mitochondrial ferritin (FTMT) accumulation and markedly suppressed expression of the iron transporter ABCB7. To test the hypothesis that ABCB7 is a key mediator of ineffective erythropoiesis of RARS, we modulated its expression in hematopoietic cells. ABCB7 up and downregulation did not influence growth and survival of K562 cells.

Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.

In a previous study, we identified somatic mutations of SF3B1, a gene encoding a core component of RNA splicing machinery, in patients with myelodysplastic syndrome (MDS). Here, we define the clinical significance of these mutations in MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). The coding exons of SF3B1 were screened using massively parallel pyrosequencing in patients with MDS, MDS/MPN, or acute myeloid leukemia (AML) evolving from MDS.