bims-conane Biomed News
on Congenital anemias
Issue of 2025–07–06
eight papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. A Retrospective Study of Unmet Blood Transfusion Needs and Status of Iron Overload in 190 Transfusion-Dependent Thalassemia Patients from Southern China.
  2. Iron-Loading Anemias.
  3. Genetic Modifiers of HbF in HbAA and HbAS Women From São Tomé e Príncipe: An Association Study of Common Genetic Variants in BCL11A, MYB, HBG2, and BGLT3.
  4. Evaluating Unghosted Cells (UGC): An Automated Blood Cell Counter-Derived Novel Red Cell Research Parameter for Its Clinical Utility and Diagnostic Implications Across a Spectrum of Pathological Conditions.
  5. Metabolic reprogramming during ineffective erythropoiesis in β-thalassemia/HbE disease.
  6. Association of TGF-β1 -509 C > T (rs1800469) polymorphism with bone marrow failure severity in Fanconi anemia subjects.
  7. Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.
  8. Luspatercept for Transfusion-Dependent Beta-Thalassemia: Real-World Experience in a Large Cohort of Patients From Italy.
  1. Hemoglobin. 2025 Jul 02. 1-5
    A Retrospective Study of Unmet Blood Transfusion Needs and Status of Iron Overload in 190 Transfusion-Dependent Thalassemia Patients from Southern China.
    Zuzu Tang, Yaqing Zhang, Lang Qin, Yufang Gu, Haiying Li, WeiPing Wei, Zhen Lu, Shuqing Huang, Yaoyun Li, Xuehua Zhou, Haifeng Liao, Yuanxiang Nong, Shuzhi Pan, Weijie Chen, Yuhua Ye, Xiangmin Xu, Xinhua Zhang, Lihong Zeng, Li Wang.
      
    DOI:  https://doi.org/10.1080/03630269.2025.2517134
  2. Adv Exp Med Biol. 2025 ;1480 145-161
    Iron-Loading Anemias.
    Maayan V Levy, Yelena Z Ginzburg.
      Erythropoiesis is a process by which red blood cells (RBCs) are produced in the adult bone marrow. It involves the differentiation of erythroid progenitor cells into mature RBCs, which transport oxygen from the lungs to all cells in the body. Erythropoiesis is a complex process with a nuanced crosstalk of regulation involving hormones, cytokines, and growth factors. In recent years, multiple sources of evidence have increased our understanding of the molecular mechanisms that coordinate erythropoiesis to enable the daily production of approximately 200 billion RBCs. These advances have shed light on the pathophysiology in a variety of diseases, i.e., iron-loading anemias, and are paving the way for novel therapeutic strategies in preclinical and clinical development to treat such dyserythropoietic disorders. This chapter elucidates our current understanding of iron-loading anemias in general and specifically in β-thalassemia and myelodysplastic syndrome (MDS), describes the current cutting-edge understanding in pathophysiology, and delineates what novel therapies are currently being developed to target these disorders.
    Keywords:  Erythroferrone (ERFE); Ineffective erythropoiesis; Iron overload; Myelodysplastic syndromes (MDS); β-thalassemia
    DOI:  https://doi.org/10.1007/978-3-031-92033-2_11
  3. Front Biosci (Schol Ed). 2025 Jun 25. 17(2): 38388
    Genetic Modifiers of HbF in HbAA and HbAS Women From São Tomé e Príncipe: An Association Study of Common Genetic Variants in BCL11A, MYB, HBG2, and BGLT3.
    Licínio Manco, Afonso Marques Morais, Sara Miguel Almeida, Inês Salgado, Luís Relvas, Celdidy Monteiro, Guilherme Queiroz, Celeste Bento.
       BACKGROUND: While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the HBB gene cluster, the BCL11A gene, and the HBS1L-MYB (HMIP) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in BCL11A (rs11886868 and rs1427407), HMIP (rs66650371 and rs4895441), HBG2 (rs7482144), and BGLT3 (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).
    METHODS: A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.
    RESULTS: Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two BCL11A SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (p = 0.00018 and p = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for BCL11A SNPs rs11886868 and rs1427407, as well as for the HBG2 rs7482144 and BGLT3 rs7924684 variants. We found no association between HbF levels and the two HMIP variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (p > 0.05).
    CONCLUSIONS: We successfully replicated the association between the two well-known BCL11A SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs HBG2 (rs7482144) and BGLT3 (rs7924684).
    Keywords:  BCL11A; BGLT3; HBG2-XmnI; HMIP; HbF regulation; São Tomé e Príncipe
    DOI:  https://doi.org/10.31083/FBS38388
  4. Int J Lab Hematol. 2025 Jun 29.
    Evaluating Unghosted Cells (UGC): An Automated Blood Cell Counter-Derived Novel Red Cell Research Parameter for Its Clinical Utility and Diagnostic Implications Across a Spectrum of Pathological Conditions.
    Anita Giri, Praveen Sharma, Dikshat Gopal Gupta, Minakshi Gupta, Pulkit Rastogi, Srinivasan Peyam, Aashima Arora, Alka Rani Khadwal, Elena Sukacheva, Prashant Sharma, Reena Das.
       INTRODUCTION: Automated estimation of poikilocytes by automated hematology analyzers remains challenging. The unghosted cells (UGC) parameter in Beckman Coulter UniCel DxH 800 analyzers has been reported to correlate with target cells and other conditions with increased erythrocytic osmotic resistance like microcytosis/hypochromia, sickle cells, and post splenectomy. We assessed UGCs' reference range and potential clinical utility in a specialist hematology laboratory.
    MATERIALS AND METHODS: We prospectively enrolled 520 participants, encompassing healthy individuals (n = 45), β-thalassemia trait (n = 196), hemoglobinopathies (n = 104), iron deficiency anemia (n = 88), liver disease (n = 46), spherocytosis (n = 18), and neonatal cord blood samples (n = 23). Peripheral blood EDTA samples were analyzed. UGC data were correlated with peripheral smear findings. In addition, red cell parameters including UGC were compared to differentiate β-thalassemia trait (βTT) from iron deficiency.
    RESULTS: UGCs were undetectable or present in very low numbers in healthy individuals (range 0%-0.01%). They demonstrated a significant positive correlation with manual target cell counts on peripheral smear (correlation coefficient, r = 0.64, p < 0.001). The highest UGC levels were observed in those with liver disease, with a median value of 0.395% (range: 0%-8.23%). All non-control subgroups, except for spherocytosis, showed significantly increased UGC% (p < 0.0001) vis-à-vis healthy individuals. A novel formula at a cut-off of 0.77 demonstrated 86.22% sensitivity and 93.10% specificity in differentiating βTT and IDA.
    CONCLUSIONS: UGC% represents an innovative, automated hematological red cell research parameter capable of screening target cells and quantifying them. UGC shows significant potential for clinical diagnostic applications across a wide range of disorders characterized by target cells, facilitating differential diagnoses in clinical practice.
    Keywords:  Coulter; UGC; iron deficiency anemia; target cells; thalassemia; unghosted red cells
    DOI:  https://doi.org/10.1111/ijlh.14521
  5. Exp Mol Pathol. 2025 Jul 01. pii: S0014-4800(25)00030-9. [Epub ahead of print]143 104980
    Metabolic reprogramming during ineffective erythropoiesis in β-thalassemia/HbE disease.
    Chanyanat Sukhuma, Donny Nauphar, Khanita Nuamsee, Wasinee Kheansaard, Kittiphong Paiboonsukwong, Alisa Wilantho, Chumpol Ngamphiw, Pornthip Chaichompoo, Sissades Tongsima, Saovaros Svasti, Phatchariya Phannasil.
      Ineffective erythropoiesis, the main cause of anemia in β-thalassemia disease, is characterized by dramatic expansion of erythroblasts and increased erythroblast cell death. The absence or reduction of β-globin chains causes an accumulation of excess α-globin chains and generates cytotoxic reactive oxidant species, resulting in erythroblast cell death. Metabolism provides energy, building blocks for macromolecule synthesis, and cofactors for antioxidative defense systems. We hypothesized that β-thalassemia erythroblasts might alter their metabolism to cope with increased proliferation and cellular stress. Herein, transcriptomic analysis of basophilic and polychromatic erythroblasts isolated from bone marrow obtained from β-thalassemia/HbE patients showed the global up-regulation of metabolic genes in glycolysis, TCA cycle, pentose phosphate pathway, ATP, and fatty acid synthesis pathway. The expression of metabolic genes during terminal erythropoiesis was further determined by PCR array and RT-qPCR in erythroblast culture obtained from β-thalassemia/HbE patients with mild and severe symptoms. The increased expression of enolase1, isocitrate dehydrogenase 1, and bisphosphoglycerate mutase was observed in mild cases compared to severe patients, suggesting that mild patients might modulate metabolic flux for cellular stress defense mechanisms, reducing disease severity. Moreover, the role of BPGM in regulating erythroid differentiation was demonstrated in K562 cells. Inhibition of BPGM promotes cell differentiation in K562 cells. Understanding metabolic reprogramming in thalassemia erythropoiesis opens new therapeutic approaches for β-thalassemia/HbE treatment. Further research is needed to explore how metabolism affects ineffective erythropoiesis and supports thalassemic erythroblasts' high proliferation and oxidative stress defense.
    Keywords:  Ineffective erythropoiesis; Metabolic genes; Metabolic reprogramming; Metabolism; Β-Thalassemia/HbE disease
    DOI:  https://doi.org/10.1016/j.yexmp.2025.104980
  6. Mol Biol Rep. 2025 Jun 28. 52(1): 651
    Association of TGF-β1 -509 C > T (rs1800469) polymorphism with bone marrow failure severity in Fanconi anemia subjects.
    Niranjan Sheshrao Chavan, Merin George, Somprakash Dhangar, Shraddha Hadkar, Jagadeeshwar Ghatanatti, Aruna Rajendran, Sandeep Nemani, Sangeeta Mudaliar, Mamta Manglani, Pranoti Kini, Babu Rao Vundinti.
       BACKGROUND: Fanconi anemia (FA) is a rare inherited genetic disorder marked by defective DNA repair mechanisms, bone marrow failure (BMF), and increased cancer susceptibility. Cytokines, specifically TGF-β are reported to be critical in FA pathophysiology, and their increased level leads to exacerbated BMF; however, the effect of genetic variability on TGF-β expression and clinical outcome remains poorly understood. This study investigates the impact of TGF-β1-509 C > T polymorphism (rs1800469) on TGF-β expression.
    METHODS: The study was carried out on 61 confirmed diagnosed FA subjects, using chromosomal breakage studies and molecular analysis. Genotyping was performed via Sanger sequencing, and TGF-β1 quantification was carried out using ELISA and qRT-PCR. Chi-square or Fisher's exact tests, and ANOVA (or Kruskal-Wallis tests in non-normal distributions) were performed to calculate the statistical significance.
    RESULTS: All 61 FA subjects showed a high frequency of chromosomal breaks and mutations in FA complementation groups. The genotyping of TGF-β1-509 C > T polymorphism (rs1800469) revealed the following genotype frequencies: CC (41%), CT (44.2%) and TT (14.8%). The allelic frequency was C = 0.63 for the major allele and T = 0.37 for the minor allele. The TGF-β1 expression was genotype dependent. Individuals with the CC genotype showed maximum levels of TGF-β1 expression, while CT heterozygotes showed intermediate expression, and the TT homozygotes showed significantly lower levels of mRNA and protein expression. Notably, the TT genotype, associated with reduced TGF-β1 expression, correlated with improved haematological parameters, including higher haemoglobin and neutrophil count, suggesting a protective role against severe BMF.
    CONCLUSIONS: This study suggests rs1800469 polymorphism as a critical modifier of TGF-β1 expression in FA, and suggests that the TT genotype may confer a protective advantage by reducing the severity of bone marrow failure.
    Keywords:  Bone marrow failure; Fanconi anemia; Gene expression; Genotype-phenotype correlation; TGF-β1; rs1800469
    DOI:  https://doi.org/10.1007/s11033-025-10759-x
  7. Nat Commun. 2025 Jul 01. 16(1): 5639
    Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.
    Maria Rosa Lidonnici, Giulia Chianella, Nicole Mende, Hugo P Bastos, Matteo Barcella, Ivan Merelli, Mariangela Storto, Valentina Romeo, Francesca Tiboni, Samantha Scaramuzza, Claudia Rossi, Laura Raggi, Annamaria Aprile, Stefania Crippa, Deena Iskander, Irene Roberts, Anastasios Karamiditris, Julia Keith, Christophe Lechauve, Mitchell J Weiss, Nicola K Wilson, Berthold Göttgens, Maria Ester Bernardo, Fabio Ciceri, Alessandro Aiuti, Sarah Marktel, Elisa Laurenti, Giuliana Ferrari.
      The hematopoietic stem cell and multipotent progenitor (HSC/MPP) pool dynamically responds to stress to adapt blood output to specific physiological demands. In β-thalassemia (Bthal), severe anemia and ineffective erythropoiesis generate expansion of erythroid precursors and a chronic stress status in the bone marrow (BM) microenvironment. However, the response to the BM altered status at the level of the HSC/MPP compartment in terms of lineage commitment has not been investigated. Bulk and single-cell RNA-sequencing reveal that Bthal HSCs/MPPs are expanded and activated with enhanced priming along the whole Ery differentiation trajectory. Consistently, HSC/MPP showed an altered TGFβ expression and autophagy transcriptional signatures along with a declined dormancy state. We discovered that the altered TGFβ signaling fosters the Ery potential of HSCs by reducing their autophagic levels, and in vivo stimulation of autophagy is sufficient to rescue the imbalance of the HSC compartment. Our findings identify the interplay between TGFβ and HSC autophagy as a key driver in the context of non-malignant hematopoiesis.
    DOI:  https://doi.org/10.1038/s41467-025-60676-7
  8. Am J Hematol. 2025 Jul 01.
    Luspatercept for Transfusion-Dependent Beta-Thalassemia: Real-World Experience in a Large Cohort of Patients From Italy.
    Raffaella Origa, Barbara Gianesin, Antonietta Zappu, Anna Rita Denotti, Mary Ann Di Giorgio, Roberta Sciortino, Irene Motta, Daniele Lello Panzieri, Rosamaria Rosso, Anna Bulla, Martina Culcasi, Anna Maria Pasanisi, Lucia De Franceschi, Rosario Di Maggio, Valeria Maria Pinto, Paola Maria Grazia Sanna, Paolo Ricchi, Giovan Battista Ruffo, Francesca Schieppati, Domenico Roberti, Giovanni Battista Ferrero, Elisa De Michele, Francesco Arcioni, Ilaria Fotzi, Sarah Marktel, Antonella Poloni, Giulia Soverini, Epifania Rita Testa, Giusy Cabiddu, Carmelo Fortugno, Antonia Gigante, Francesca Polese, Davide Rapezzi, Antonella Sau, Gian Luca Forni, Maria Domenica Cappellini, Filomena Longo.
      
    Keywords:  extramedullary hematopoiesis; luspatercept; real‐world setting; thromboembolism; transfusion‐dependent thalassemia
    DOI:  https://doi.org/10.1002/ajh.27758
This page is being maintained by Thomas Krichel. It was last updated on 2025‒07‒12 at 11:28.