ASXL1 deficiency causes epigenetic dysfunction, combined immunodeficiency, and EBV-associated lymphoma.

Inborn errors of immunity (IEIs) are caused by deleterious variants in immune-related genes. ASXL1 is an epigenetic modifier not previously linked to an IEI. Clonal hematopoiesis and hematologic neoplasms often feature somatic ASXL1 variants, and Bohring-Opitz syndrome, a neurodevelopmental disorder, is caused by heterozygous truncating ASXL1 variants.

A longitudinal single-cell atlas of treatment response in pediatric AML.

Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse.

Processing and Cryopreservation of Blood, Cancer Tissues, and Cancer Cells for Viable Biobanking.

Biorepositories of fresh frozen and formalin-fixed paraffin-embedded tissues have been foundational to many molecular cancer research studies. Collections of these materials, however, do not enable the establishment of short-term cultures, cell lines, or patient-derived xenograft models for functional studies. Also, intact dissociated cells that are required for some single-cell analyses cannot be obtained from these material types.

Biobank Awareness Changes Opinions of Adolescents and Parents on Participation and Practices.

To evaluate barriers and facilitators of pediatric biobank participation, we studied whether increased awareness of participants about pediatric biobanking changes their opinions on biobanking practices and their willingness to participate in biobanks. Adolescents (14-18 years) in public schools and their parents were invited to participate in a survey either with or without viewing educational material about biobanking before completing the survey. Questions included willingness to donate, consenting practices and use of specimens.

A cross-standardized flow cytometry platform to assess phenotypic stability in precursor B-cell acute lymphoblastic leukemia (B-ALL) xenografts.

With the continued poor outcome of relapsed acute lymphoblastic leukemia (ALL), new patient-specific approaches for disease progression monitoring and therapeutic intervention are urgently needed. Patient-derived xenografts (PDX) of primary ALL in immune-deficient mice have become a powerful tool for studying leukemia biology and therapy response. In PDX mice, the immunophenotype of the patient's leukemia is commonly believed to be stably propagated.

Detectable Unmetabolized Folic Acid and Elevated Folate Concentrations in Folic Acid-Supplemented Canadian Children With Sickle Cell Disease.

Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a variant (rs344) in the gene encoding the β-globin subunit of hemoglobin. Chronic hemolytic anemia and increased erythropoiesis and RBC turnover in individuals with SCD can result in increased needs for folate and other B-vitamins. We assessed B-vitamin status, and the distribution of folate forms, including unmetabolized folic acid (UMFA), in Canadian children with SCD supplemented with 1 mg/d folic acid (current routine practice).

Ethical Challenges for Pediatric Biobanks.

Biobank participation of children is an ethically complicated process as the vulnerability of this population is a concern throughout the entire process of biobanking. Some ethical issues are more prominent in pediatric biobanking and may not need to be considered in biobanking of adult specimens and data. These include assent, reconsent at the age of majority, capacity to consent, and consequences of genetic results on the child and family members.

Clinical and laboratory features associated with myeloperoxidase expression in pediatric B-lymphoblastic leukemia.

Background: B-lymphoblastic leukemia (B-ALL) is the most common childhood malignancy, and its diagnosis requires immunophenotypically demonstrating blast B cell lineage differentiation. Expression of myeloperoxidase (MPO) in B-ALL is well-described and it has been recognized that a diagnosis of mixed phenotype acute leukemia should be made cautiously if MPO expression is the sole myeloid feature in these cases. We sought to determine whether MPO expression in pediatric B-ALL was associated with differences in laboratory, immunophenotypic, or clinical features.

Prevalence of Vitamin D Deficiency Varies Widely by Season in Canadian Children and Adolescents with Sickle Cell Disease.

Sickle cell disease (SCD) is an inherited disorder caused by a variant (334) in the β-globin gene encoding hemoglobin. Individuals with SCD are thought to be at risk of vitamin D deficiency. Our aim was to assess serum 25-hydroxyvitamin D (25OHD) concentrations, estimate deficiency prevalence, and investigate factors associated with 25OHD concentrations in children and adolescents with SCD attending BC Children's Hospital in Vancouver, Canada.

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. A- deficiency is characterized by the co-inheritance of 376 and 202 variants and is common in sub-Saharan Africa.

The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial.

Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy. We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic.

Business Planning for a Campus-Wide Biobank.

Biobanks are resources that facilitate research. Many biobanks exist around the world, but most tend to focus on a specific disease or research area. BC Children's Hospital and BC Women's Hospital are located on the same campus (Oak Street Campus) in Vancouver, BC, Canada.

How Biobanks Are Assessing and Measuring Their Financial Sustainability.

As guest editors of this sustainability issue of Biopreservation and Biobanking focused on business planning, utilization, and marketing, we invited a number of experts from different sectors of the biobanking arena to provide their views on business planning issues. Each expert was asked to provide a brief background statement on their biobanks, to build a context to understand their answers to the sustainability questions. We hope that these insights and experiences can provide valuable considerations and ideas for other biobanks who wish to develop or refine their own business plans, measure their utilization rates, and work toward financial sustainability.

Comparison of four immunoassays to measure serum ferritin concentrations and iron deficiency prevalence among non-pregnant Cambodian women and Congolese children.

Background: Global standardization of ferritin assays is lacking, which could have direct implications on the accurate measurement and comparability of ferritin concentration and iron deficiency (ID) prevalence rates in at-risk populations.

Methods: We measured serum ferritin concentrations using four immunoassays: the s-ELISA and the AxSYM™ analyzer were compared among 420 non-pregnant Cambodian women; the Centaur® XP analyzer, s-ELISA, and AxSYM™ analyzer were compared among a subset of 100 Cambodian women; and the s-ELISA and the Elecsys® 2010 analyzer were compared among 226 Congolese children aged 6-59 months.

Results: Median ferritin concentrations (adjusted for inflammation) ranged between 48 and 91 μg/L among Cambodian women and between 54 and 55 μg/L among Congolese children.

Opinions of Adolescents and Parents About Pediatric Biobanking.

Purpose: A biobank is defined as "a facility for the collection, preservation, storage and supply of biological samples and associated data, which follows standardized operating procedures and provides material for scientific and clinical use." The practice of biobanking must consider the best interests of participants, which is especially complicated in the pediatric setting, where parents or guardians are responsible for consent of their children. Age of participant assent, consent, and reconsent at the age of majority are some of the issues which need to be addressed.

The Homozygous Hemoglobin EE Genotype and Chronic Inflammation Are Associated with High Serum Ferritin and Soluble Transferrin Receptor Concentrations among Women in Rural Cambodia.

Background: Ferritin and soluble transferrin receptor (sTfR) concentrations are commonly used to assess iron deficiency (ID); however, they are influenced by multiple factors.

Objectives: We assessed associations between numerous variables and both ferritin and sTfR concentrations in Cambodian women and compared ID prevalence through the use of study-generated correction factors (CFs) for ferritin with those from a published meta-analysis.

Methods: Venous blood from 450 women (aged 18-45 y) was assessed for hemoglobin (Hb), ferritin, sTfR, retinol binding protein, folate, vitamin B-12, C-reactive protein, α-1 acid glycoprotein (AGP), and genetic Hb disorders.

Elevated levels of iron in groundwater in Prey Veng province in Cambodia: a possible factor contributing to high iron stores in women.

Iron is a natural element found in food, water and soil and is essential for human health. Our aim was to determine the levels of iron and 25 other metals and trace elements in groundwater from 22 households in Prey Veng, Cambodia. Water analyses were conducted using inductively coupled plasma-mass spectrometry and optical emission spectrometry.

Evaluation of two methods to measure hemoglobin concentration among women with genetic hemoglobin disorders in Cambodia: a method-comparison study.

Background: Genetic hemoglobin (Hb) E variants are common in Cambodia and result in an altered and unstable Hb molecule. We evaluated two methods to measure Hb concentration among individuals with and without Hb variants using a hemoglobinometer (HemoCue) and a hematology analyzer (Sysmex XT-1800i).

Methods: We determined the bias and concordance between the methods among 420 Cambodian women (18-45 y).

Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural prey Veng, Cambodia.

Background: Anemia is common in Cambodian women. Potential causes include micronutrient deficiencies, genetic hemoglobin disorders, inflammation, and disease.

Objectives: We aimed to investigate factors associated with anemia (low hemoglobin concentration) in rural Cambodian women (18-45 y) and to investigate the relations between hemoglobin disorders and other iron biomarkers.