bims-conane 2025-10-05 papers

Am J Hematol. 2025 Oct 03.

Quantifying Morbidity Risk Attributed to Red-Cell Transfusion Volume in Optimally Transfused Patients With β-Thalassemia.

In the long-term follow up study (de-LIGHT), the magnitude of transfusion burden was significantly and incrementally associated with morbidity development in transfusion-dependent patients achieving target hemoglobin thresholds.

Keywords: complications; thalassemia; transfusion

DOI: https://doi.org/10.1002/ajh.70100

Ann Hematol. 2025 Oct 01.

Codanin-1, defective in congenital dyserythropoietic anemia I (CDA-I), regulates erythroid differentiation.

Linette Bosques, Susree Modepalli, Arvindhan Nagarajan, Caroline Tang, Sandra Martínez-Morilla, Nur-Taz Rahman, Sameet S Mehta, Diane S Krause, Hannah Tamary, Patrick G Gallagher, Shilpa M Hattangadi, Gary M Kupfer.

BACKGROUND: Congenital dyserythropoietic anemia type I (CDA-I) is an autosomal recessive disorder marked by ineffective erythropoiesis, abnormal morphology of bone marrow erythroblasts, and iron overload. Most cases of CDA-I are caused by mutations in the CDAN1 gene, which encodes a ubiquitous protein of unknown function, Codanin-1.
METHODS: To investigate the role of Codanin-1 in the molecular pathways involved in CDA-I, we developed erythroid models using human K562 cells and primary human CD34 + cells from mobilized peripheral blood.
RESULTS: Here we show that Codanin-1 expression is required for erythroid progenitor development and normal erythroid cell differentiation. Erythroid cells lacking Codanin-1 demonstrated morphologic changes similar to those observed in CDA-I. Global gene expression changes after Codanin-1 knockdown revealed alterations in a set of key erythroid genes. In particular, the AHSP gene, which showed reduced mRNA and protein expression levels after Codanin-1 knockdown, also demonstrated increased Codanin-1 occupancy at its gene regulatory region by chromatin immunoprecipitation coupled to high-throughput sequencing.
CONCLUSION: In summary, using cell models recapitulating many features of CDA-I, we have studied and confirmed the importance of Codanin-1 during erythroid differentiation and provide mechanistic insight into how loss of Codanin-1 expression results in CDA-I.

Keywords: Benzidine; Binuclearity; Codanin-1; Erythroid; Hemoglobin

DOI: https://doi.org/10.1007/s00277-025-06540-6

Blood Res. 2025 Sep 29. 60(1): 51

Molecular spectrum and carrier frequency of deletional hereditary persistence of fetal hemoglobin and delta-beta thalassemia in Malaysia.

Faidatul Syazlin Abdul Hamid, Sabariah Md Noor, Mei I Lai, Samsol Kamal Mohd Bahari, Ezalia Esa, Ermi Neiza Mohd Sahid, Norafiza Mohd Yasin, Yuslina Mat Yusoff.

PURPOSE: Thalassemia is a major public health concern in Southeast Asia, particularly in Malaysia, where a high carrier rate places significant pressure on healthcare systems. Hereditary Persistence of Fetal Hemoglobin (HPFH) and delta-beta (δβ) thalassemia are genetic conditions associated with elevated levels of fetal hemoglobin (Hb F). This study aimed to determine the frequency of common beta (β)-globin gene cluster deletions among Malaysian carriers of HPFH or δβ thalassemia, while also providing an overview of the thalassemia burden in the region.
METHODS: A retrospective study was conducted on 534 blood samples submitted to the Institute for Medical Research (IMR), Malaysia, for β-thalassemia genotyping between January 2017 and December 2019. Demographic data, including full blood count parameters and hemoglobin (Hb) analysis, were retrieved. Deoxyribonucleic acid (DNA) was extracted and analyzed using Multiplex Gap-Polymerase Chain Reaction (PCR) to detect large deletions in the β-globin gene cluster.
RESULTS: Seven distinct deletions were identified among the 534 heterozygous carriers. The two most common deletions were Gγ(Aγδβ)°-thalassemia Siriraj I (~ 118 kilobase pairs [kb]) and δβ°-thalassemia Thai (~ 12.5 kb), accounting for 30.0% and 29.8% of cases, respectively. The HPFH-6 deletion was observed in 20.0% of cases, followed by Gγ(Aγδβ)°-thalassemia Asian-Indian Inversion-Deletion (Inv/Del) (14.2%), Gγ(Aγδβ)°-thalassemia Chinese (~ 100 kb) (4.3%), HPFH-3 (0.9%), and Gγ(Aγδβ)°-thalassemia Asian (~ 49.3 kb) (0.7%). The ethnic distribution showed a predominance among Malay patients (93.4%), with specific deletions suggesting ethnic clustering. Genotype-phenotype analysis revealed notable variations in hematological parameters: carriers of HPFH-3 had the highest Hb F levels (25.3 ± 3.1%) as measured by high-performance liquid chromatography (HPLC) and showed the least severe microcytosis, while carriers of δβ°-thalassemia Thai (~ 12.5 kb) demonstrated more pronounced hematological abnormalities. Findings were consistent with previous reports from Southeast Asia, underscoring the importance of incorporating molecular diagnostics into national screening programs. Although Multiplex Gap-PCR is robust, further studies using Next-Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) are recommended to detect rare or undetected mutations.
CONCLUSIONS: This study provides crucial data on the molecular spectrum of HPFH and δβ thalassemia in Malaysia, contributing to improved diagnostic strategies and genetic counselling. Future research should explore additional genetic variants to enhance national thalassemia prevention programs.

Keywords: Beta thalassemia; Delta; Globin gene cluster; Hereditary Persistence of Fetal Hemoglobin; High Hb F; Large deletions of the β; Multiplex Gap; PCR; Polymerase chain reaction

DOI: https://doi.org/10.1007/s44313-025-00100-7

Curr Res Transl Med. 2025 Sep 09. pii: S2452-3186(25)00051-0. [Epub ahead of print]73(4): 103542

Successful treatment of congenital sideroblastic anemia with low-dose decitabine in a patient with NDUFB11 gene mutation (c.276_278del): A case report.

Juan Wang, Heng Li, Nan Lv, Min Wang, Hongyu Zhao.

BACKGROUND: Congenital sideroblastic anemias (CSAs) are an inherited group of blood disorders due to defects of mitochondrial proteins. The NDUFB11 gene is essential for the assembly of mitochondrial complex Ⅰ protein. Mutations in the NDUFB11 gene can cause sideroblastic anemia with hyperlacticemia, microphthalmia, cardiomyopathy and encephalomyopathy with limited therapeutic options.
CASE PRESENTATION: We reported a 35-year-old man with congenital sideroblastic anemia, skeletal dysplasias and hyperlacticemia. The skeletal muscle stains indicated probability of mitochondrial disorders. By whole-exome sequencing, we identified a mutation (c.276_278delCTT) in NDUFB11 gene in this patient which was inherited from his mother. He was unresponsive to the treatment of vitamin B2, vitamin B6, Coenzyme Q10, idebenone, or EPO but achieved hemoglobin concentration rise, transfusion independence and improvement of quality life after treated with low dose decitabine.
CONCLUSIONS: We proposed that epigenetic factors might play a role in pathogenesis in patients with c.276_278del (p.F93del) mutation in NDUFB11 gene and low dose decitabine may be a novel treatment in CSA patients with c.276_278del (p.F93del) mutation in NDUFB11 gene.

Keywords: Congenital sideroblastic anemias; Low dose decitabine; Mitochondrial disorder; NDUFB11; Whole-exome sequencing

DOI: https://doi.org/10.1016/j.retram.2025.103542