bims-conane 2026-05-10 papers

Pediatr Blood Cancer. 2026 May 09. e70363

Germline TP53 Mutations Causing Diamond-Blackfan Anemia: A French Report.

Rafael Moisan, Lydie Da Costa, Ludivine David Nguyen, Heloise Chosseler, Audrey Riquet, Benedicte Bruno, Melissa Barbati.

Diamond-Blackfan anemia is a rare congenital erythroblastopenia typically caused by mutations in ribosomal protein genes. Recently, gain-of-function mutations in TP53 have been identified as a novel cause of Diamond-Blackfan anemia. We report two French patients who both harbored a heterozygous TP53 deletion (NM_000546.5: c.1077delA; p.(Ser362AlafsTer8)). They exhibited normocytic anemia, transient neutropenia at presentation, and distinct neurological impairments. Neither patient responded to a corticosteroid trial. One patient underwent hematopoietic stem cell transplantation from a matched sibling donor and remained transfusion-independent at last follow-up. This study emphasizes the complexity of TP53-associated Diamond-Blackfan anemia syndrome and presents the only patient to date cured by hematopoietic stem cell transplantation.

Keywords: DBAS‐Other; Diamond–Blackfan anemia; TP53; hematopoietic stem cell transplantation; inherited bone marrow failure; neurological impairment

DOI: https://doi.org/10.1002/1545-5017.70363

Antioxidants (Basel). 2026 Apr 14. pii: 482. [Epub ahead of print]15(4):

Iron Overload-Associated Oxidative Stress and Immune Cell Dysfunction in Thalassemia: Integrative Analysis of Hematological, Biochemical, and Flow Cytometric Biomarkers.

Sirichai Srichairatanakool, Narisara Paradee, Bishant Pokharel, Yanping Zhong, Onsaya Kerdto, Wuttipat Kiratipaisarl, Adisak Tantiworawit, Chatree Chai-Adisaksopha, Somdet Srichairatanakool.

Thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic hemolysis, and transfusion-related iron overload, which collectively contribute to oxidative stress and organ dysfunction. The present study aimed to investigate the relationships between iron metabolism, oxidative stress biomarkers, and immune cell function across different clinical conditions. Peripheral blood samples were obtained from healthy individuals and patients with iron deficiency anemia, obesity, thalassemia trait (TT), β-thalassemia HbE (BTE), and β-thalassemia major (BTM). Hematological parameters were measured using automated hematology analyzers, while biochemical indicators, including liver enzymes and bilirubin, were determined using clinical chemistry assays. Iron overload was evaluated using serum iron parameters and T2*-weighted magnetic resonance imaging. Oxidative stress biomarkers, including reduced glutathione, thiobarbituric acid-reactive substances, and total antioxidant capacity, were assessed spectrophotometrically. Flow cytometric analysis was used to measure reactive oxygen species, redox-active iron, and lipid peroxide levels in granulocytes and lymphocytes. Thalassemia patients exhibited severe anemia, elevated liver enzymes, increased bilirubin levels, and significant alterations in iron metabolism compared with healthy controls. Hepatic iron accumulation was more common than cardiac iron deposition, particularly in BTE patients. Granulocyte oxidative burst activity was significantly reduced in thalassemia patients, whereas lymphocyte responses remained relatively preserved. Increased variability in glutathione levels suggested activation of intracellular antioxidant defense mechanisms in response to chronic oxidative stress. These findings highlight the complex interplay between iron overload, oxidative stress, and the immune cell dysfunction associated with thalassemia, thereby providing insights into improved monitoring and therapeutic strategies.

Keywords: antioxidant defense; granulocytes; iron overload; oxidative stress; reactive oxygen species; redox-active iron; thalassemia

DOI: https://doi.org/10.3390/antiox15040482

Sci Rep. 2026 May 06.

Molecular and hematological characterization of thalassemia and hemoglobinopathies among pediatric patients in northern Lao People's Democratic Republic.

Volapheth Kanyasone, Pichpimon Pakpuak, Supitsaraporn Satewin, Anupong Pansuwan, Kritsada Singha, Attawut Chaibunruang, Hataichanok Srivorakun, Supan Fucharoen, Annkham Thammaseng, Sengmany Sengphachan, Hame Thiphalack, Anousine Phonedala, Supawadee Yamsri.

Thalassemia and hemoglobinopathies are highly prevalent in the Lao People's Democratic Republic (Lao PDR). Luang Prabang Province represents an ethnically diverse area with a high burden of pediatric anemia, but the molecular and hematological characteristics of thalassemia in this setting have not been systematically described. This hospital-based cross-sectional study included consecutive pediatric patients encountered at the Lao Friends Hospital for Children, Luang Prabang, between August and November 2025. Leftover EDTA-anticoagulated blood specimens and corresponding clinical data were analyzed. Hemoglobin analysis was performed using capillary zone electrophoresis, and molecular characterization of α- and β-globin gene defects was conducted using PCR-based assays. A total of 206 pediatric patients were recruited. β-thalassemia disease accounted for 51.9% of hospital presentations (n = 107), while 26.2% of patients had α-thalassemia diseases (n = 54), and the remaining cases comprised combined α- and β-thalassemia diseases (n = 38, 18.9%). Molecular analysis identified as many as 40 distinct thalassemia genotypes, indicating substantial genetic heterogeneity. Among α-thalassemia disease, non-deletional Hb H disease, predominantly associated with the --SEA/αCSα genotype, was the most frequent presentation. Among β-thalassemia disease, β⁰/βE was the most common genotype. At the molecular level, hemoglobin E was the most frequent β-globin allele, followed by the codons 41/42 (-TTCT), codon 17 (A > T), and promoter - 28 mutations (A > G). Hematological findings demonstrated moderate to severe anemia across clinically significant thalassemia syndromes. The first hospital-based molecular and hematological characterization of pediatric thalassemia in northern Lao PDR demonstrates genotypic and phenotypic heterogeneities, with clinically significant β-thalassemia and non-deletional α-thalassemia. These findings provide important evidence to support more accurate diagnostic approaches and inform thalassemia screening and prevention strategies in Lao PDR.

Keywords: Anemia; Hemoglobinopathies; Lao PDR; Molecular diagnosis; Pediatric; Thalassemia

DOI: https://doi.org/10.1038/s41598-026-51509-8

Int J Lab Hematol. 2026 May 04.

Iron Overload: Pathophysiology, Diagnosis and Monitoring.

Elena Chatzikalil, Polyxeni Delaporta, Konstantinos Bistas, Antonis Kattamis.

Iron overload is associated with significant health risks, underscoring the importance of understanding its pathophysiology as well as establishing accurate diagnostic and monitoring methods. Chronic iron overload is associated with either genetic disorders characterized by excessive iron accumulation (hereditary hemochromatosis), or is secondary to diseases of ineffective erythropoiesis and/or requiring regular blood transfusions (like thalassemia, sickle cell disease, myelodysplastic syndromes). Diagnosis is based on clinical suspicion, corroborated by laboratory findings such as elevated serum ferritin and transferrin saturation, along with imaging techniques (magnetic resonance imaging) which facilitate non-invasive assessment of iron levels in parenchymal organs. Elevated ferritin and transferrin saturation and exclusion of secondary causes should prompt genetic evaluation for hereditary disorders predisposing iron overload. Chronic systemic iron overload causes progressive tissue iron accumulation, leading to severe clinical implications, including myocardial dysfunction, liver cirrhosis, and increased risk of hepatocellular carcinoma. Monitoring includes evaluating iron overload indices (serum ferritin, transferrin saturation, liver and heart iron concentration) along with serum and urine indices of parenchymal organ damage at different timepoints regarding the type of disease, patient's age, severity and response to treatment, and aims in improving disease progression and preventing complications. This article provides a comprehensive overview of the pathophysiologic mechanisms and the diagnostic and monitoring techniques of iron overload, in order to revise current knowledge and to raise clinical awareness for effective management.

Keywords: ferritin; hemochromatosis; iron overload; thalassemia; transferrin saturation

DOI: https://doi.org/10.1111/ijlh.70132