Inconsistency in ferritin reference intervals across laboratories: a major concern for clinical decision making.

Objectives: Iron deficiency anemia is a significant global health concern, diagnosed by measuring hemoglobin concentrations in combination with plasma ferritin concentration. This study investigated the variability in ferritin reference intervals among laboratories in the Netherlands and examined how this affects the identification of iron-related disorders.

Methods: Ferritin reference intervals from 52 Dutch ISO15189-certified medical laboratories were collected.

Automated tools for identifying the causes of anaemia in general practices are particularly advantageous for patients who do not fit the typical profile.

Background: The Dutch guideline algorithm for the analysis of anaemia in patients of general practitioners (GPs) was programmed in a Clinical Decision Support system (CDS-anaemia) to support the process of diagnosing the cause of anaemia in the laboratory. This research aims to assess the supplementary benefit provided by the automated algorithm in various demographic categories, including different sexes, age groups and severities of anaemia, in comparison to the manual diagnostic approach employed by GPs.

Methods: This was a retrospective cohort study of 5399 primary care patients where the cause of anaemia was diagnosed by GPs with or without the aid of CDS-anaemia within the age groups 18-44, 45-64, 65-79 and 80 and older.

[The cause of anemia is underdiagnosed in primary care].

Objective: To determine if general practitioners can diagnose the cause of anemia, based on the requested laboratory tests.

Design: Retrospective observational study.

Method: The research population consisted of 20.

The effectiveness of an automated algorithm as a tool for investigating the cause of anaemia in undiagnosed patients from general practitioners.

Background: The Dutch guideline algorithm for the analysis of anaemia in patients of general practitioners (GPs) was programmed in a Clinical Decision Support system (CDS-anaemia) to support the process of diagnosing the cause of anaemia in the laboratory. This study investigates the diagnostic yield of the automated anaemia algorithm compared to that of the manual work up by the GP.

Methods: This retrospective population-based study consisted of 2697 people ≥18 years.

The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes.

Epigenetic regulators are frequently mutated in hematological malignancies including acute myeloid leukemia (AML). Thus, the identification and characterization of novel epigenetic drivers affecting AML biology holds potential to improve our basic understanding of AML and to uncover novel options for therapeutic intervention. To identify novel tumor suppressive epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML.

The Glycolytic Gatekeeper PDK1 defines different metabolic states between genetically distinct subtypes of human acute myeloid leukemia.

Acute myeloid leukemia remains difficult to treat due to strong genetic heterogeneity between and within individual patients. Here, we show that Pyruvate dehydrogenase kinase 1 (PDK1) acts as a targetable determinant of different metabolic states in acute myeloid leukemia (AML). PDK1 AMLs are OXPHOS-driven, are enriched for leukemic granulocyte-monocyte progenitor (L-GMP) signatures, and are associated with FLT3-ITD and NPM1cyt mutations.

CombiFlow: combinatorial AML-specific plasma membrane expression profiles allow longitudinal tracking of clones.

Acute myeloid leukemia (AML) often presents as an oligoclonal disease whereby multiple genetically distinct subclones can coexist within patients. Differences in signaling and drug sensitivity of such subclones complicate treatment and warrant tools to identify them and track disease progression. We previously identified >50 AML-specific plasma membrane (PM) proteins, and 7 of these (CD82, CD97, FLT3, IL1RAP, TIM3, CD25, and CD123) were implemented in routine diagnostics in patients with AML (n = 256) and myelodysplastic syndrome (n = 33).

The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis.

Upregulation of the plasma membrane receptor IL1RAP in Acute Myeloid Leukemia (AML) has been reported but its role in the context of the leukemic bone marrow niche is unclear. Here, we studied the signaling events downstream of IL1RAP in relation to leukemogenesis and normal hematopoiesis. High IL1RAP expression was associated with a leukemic GMP-like state, and knockdown of IL1RAP in AML reduced colony-forming capacity.

Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock.

Maintenance of epigenetic modifiers is of utmost importance to preserve the epigenome and consequently appropriate cellular functioning. Here, we analyzed Polycomb group protein (PcG) complex integrity in response to heat shock (HS). Upon HS, various Polycomb Repressive Complex (PRC)1 and PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found to accumulate in the nucleolus.

Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models.

Recently, NOD-SCID IL2Rγ (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO).

Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches.

To begin to understand the mechanisms that regulate self-renewal, differentiation, and transformation of human hematopoietic stem cells or to evaluate the efficacy of novel treatment modalities, stem cells need to be studied in their own species-specific microenvironment. By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune-deficient mice, we were able to mimic the human bone marrow niche. Thus, we have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted, which covered all of the important genetic and risk subgroups.

Dynamics in N-terminal pro-brain natriuretic peptide concentration in patients with non-ST-elevation acute coronary syndrome.

Background: Although there is growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used as a powerful tool in risk prediction in patients with non-ST-elevation acute coronary syndrome (NSTEACS), the dynamic variation of serum concentrations in time is poorly understood. To gain insight into the dynamics of NT-proBNP, a study was performed using serial serum samples in patients admitted with NSTEACS.

Methods: A total of 24 patients admitted with NSTEACS was included in this study.