bims-conane 2026-03-08 papers

Exp Mol Med. 2026 Mar 04.

Orai1 acts as a novel Ca2+ signal switch, balancing erythropoiesis through KLF1 regulation.

Yoon Young Lee, Hyebin Koh, Jieun Kim, Sun-Uk Kim, Jong-Hee Lee, Chan Young Park.

Terminal erythropoiesis, the final stage of red blood cell maturation, is orchestrated by erythropoietin (EPO) and the master transcription factor, Kruppel-like factor 1 (KLF1). Recent studies highlight the importance of Ca2+ signaling in erythroid maturation; however, the underlying mechanisms remain elusive. Here we identify Orai1 as a novel EPO-responsive Ca2+ channel in erythroid cells, serving as a dynamic regulatory toggle that modulates KLF1 transcription and facilitates distinct phases of erythroid maturation. During the early stages, EPO-activated Orai1 suppresses KLF1 transcription through Ca2+-dependent NFAT2 activation and promoter binding, pausing erythroid maturation. As maturation progresses, Orai1 expression decreases, transitioning KLF1 regulation to an EPO-STAT5 pathway, thereby maintaining KLF1 expression and promoting terminal erythropoiesis. Using HUDEP-2 cells, umbilical cord blood and human pluripotent stem cell-derived CD71⁺ erythroblasts, we observed a progressive downregulation of Orai1 and reduction in intracellular Ca2+ levels during terminal maturation. The functional inactivation of Orai1 via R91W mutants and CRISPR-Cas9 knockout enhanced KLF1 expression, leading to increased erythroid-specific gene expression, accelerated erythroid maturation, higher levels of globin production and improved enucleation efficiency. This study unveils the EPO-Orai1-Ca2+-NFAT2-KLF1 axis as a critical regulatory checkpoint in erythropoiesis and highlights Orai1 downregulation as a potential strategy to enhance clinical red blood cell production by promoting erythrocyte maturation.

DOI: https://doi.org/10.1038/s12276-026-01651-0

Front Med (Lausanne). 2026 ;13 1755729

Severe bacterial infection in thalassemia patients: prevalence, predisposing factors, causative organisms and outcomes.

Ruttanaporn Taya, Adisak Tantiworawit, Harit Thongwitokomarn, Sirichai Srichairatanakool, Teerachat Punnachet, Nonthakorn Hantrakun, Pokpong Piriyakhuntorn, Thanawat Rattanathammethee, Sasinee Hantrakool, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Lalita Norasetthada, Piangrawee Niprapan, Kanda Fanhchaksai, Pimlak Charoenkwan.

Introduction: Thalassemia is one of the most common genetic blood disorders globally. Bacterial infections remain a major cause of death among affected patients. To determine prevalence, predisposing factors, causative organism, and outcomes of severe bacterial infection in thalassemia patients.
Methods: This retrospective study analyzed data from the Thalassemia Registry of the Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University (September 2013-September 2023). Thalassemia patients aged >15 years were included. Risk factors for severe bacterial infection were identified using multivariate logistic regression. Severe bacterial infection was defined as community-acquired involving a major organ, requiring parenteral antibiotics and/or surgery, and associated with a National Early Warning Score (NEWS) > 4.
Results: A total of 208 patients were enrolled (mean age 45.3 ± 16.0 years; 62.0% female; 56.7% transfusion-dependent; 36.1% splenectomy). Severe bacterial infection occurred in 43 patients (20.7%). Primary bacteremia was the most common (23.2%), with Klebsiella pneumoniae (20.9%) and Escherichia coli (13.9%) as the leading pathogens. Infection-related mortality rate was 9.3%. Significant risk factors included hematocrit <21% (OR = 3.15; 95% CI 1.32-7.50; p = 0.01), splenectomy >10 years (OR = 2.46; 95% CI 1.07-5.69; p = 0.035), diabetes mellitus (OR = 10.42; 95% CI 2.21-49.12; p = 0.03), and liver hemochromatosis (OR = 3.76; 95% CI 1.64-8.63; p = 0.002).
Conclusion: Severe bacterial infections affected 20.7% of thalassemia patients in this cohort, mainly bacteremia due to Klebsiella pneumoniae and Escherichia coli. Major risk factors were severe anemia, prolonged splenectomy, diabetes mellitus, and iron overload with liver hemochromatosis.

Keywords: Escherichia coli; Klebsiella pneumoniae; anemia; bacterial infections; thalassemia

DOI: https://doi.org/10.3389/fmed.2026.1755729

Ann Hematol. 2026 Mar 04. pii: 157. [Epub ahead of print]105(4):

Transforming the treatment of Alpha-Thalassemia: a single-center retrospective study on hematopoietic stem cell transplantation in transfusion-dependent pediatric patients.

Keywords: Alpha-Thalassemia ; Graft-versus-host disease; Hematopoietic stem cell transplantation; transfusion-dependent

DOI: https://doi.org/10.1007/s00277-026-06855-y

Cureus. 2026 Jan;18(1): e102459

Neonatal Screening for Glucose-6-Phosphate Dehydrogenase (G6PD) Gene Variants and Their Association With Hyperbilirubinemia and Phototherapy Needs.

Ismail M Alwadani, Raghad Almuslim, Mohammad Almutairi, Tahseen Elwahsh.

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in the Middle East and is a recognized risk factor for neonatal hyperbilirubinemia. However, the clinical impact of specific G6PD gene variants on hyperbilirubinemia severity remains unclear. This study aimed to determine the prevalence of G6PD gene variants among neonates at Johns Hopkins Aramco Healthcare and to evaluate their association with hyperbilirubinemia severity and phototherapy requirements.
METHODS: We conducted a retrospective cohort study of neonates diagnosed with G6PD deficiency between January 2021 and December 2023. Demographic, clinical, laboratory, and genetic data were collected from electronic medical records. G6PD variants were identified using newborn DNA screening. Associations with phototherapy requirement were assessed using chi-square and Mann-Whitney U tests. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of phototherapy.
RESULTS: Among 5,375 neonatal admissions, 572 (10.6%) neonates were diagnosed with G6PD deficiency, with a male predominance (66.6%). The c.563C>T (Mediterranean) variant was the most prevalent (93.5%). Phototherapy was required in 193 neonates (33.7%). In multivariate analysis, female sex was independently protective against phototherapy (adjusted odds ratio (AOR) = 0.239; p = 0.003), while a positive Coombs test (AOR = 8.668; p < 0.001) and the presence of two mutant G6PD gene copies (AOR = 3.890; p = 0.007) were significant independent predictors of phototherapy requirement. No significant association was observed between specific G6PD variants and the need for phototherapy.
CONCLUSION: G6PD deficiency was common in this cohort and was mainly associated with the c.563C>T mutation. A positive Coombs test and multiple gene copies were independent predictors of phototherapy, whereas specific G6PD variants were not associated with hyperbilirubinemia severity. These findings support the importance of early G6PD screening and vigilant monitoring to prevent severe neonatal hyperbilirubinemia.

Keywords: g6pd; gene variant; hyperbilirubinemia; neonate; phototherapy; saudi arabia

DOI: https://doi.org/10.7759/cureus.102459