bims-conane Biomed News
on Congenital anemias
Issue of 2025–07–20
eight papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Luspatercept versus mitapivat for non-transfusion-dependent β-thalassemia: Dare to compare?
  2. Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and β0-thalassemia/HbE individuals.
  3. Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.
  4. Quantitative assessment of red blood cell surface molecules in hereditary spherocytosis.
  5. Case-control study of maternal and fetal outcomes in beta thalassaemia trait during pregnancy.
  6. Coagulation and Fibrinolysis Dysregulation in β-Thalassemia Major: Potential Impact of Splenectomy and Medications on Thrombotic Risk.
  7. Morphologic and Electrophoretic Features of Hemoglobin Bart's Hydrops Fetalis.
  8. CRISPR-based therapeutic genome editing for inherited blood disorders.
  1. Hemasphere. 2025 Jul;9(7): e70165
    Luspatercept versus mitapivat for non-transfusion-dependent β-thalassemia: Dare to compare?
    Khaled M Musallam, Sujit Sheth, Maria Domenica Cappellini, Kevin H M Kuo, Antonis Kattamis, Yesim Aydinok, Vip Viprakasit, Ali T Taher.
      
    DOI:  https://doi.org/10.1002/hem3.70165
  2. Sci Rep. 2025 Jul 15. 15(1): 25580
    Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and β0-thalassemia/HbE individuals.
    Chokdee Wongborisuth, Pawarit Innachai, Chonticha Saisawang, Alisa Tubsuwan, Natee Jearawiriyapaisarn, Pavita Kaewprommal, Jittima Piriyapongsa, Wararat Chiangjong, Usanarat Anurathapan, Duantida Songdej, Amornrat Tangprasittipap, Suradej Hongeng.
      CRISPR/Cas9 genome editing has emerged as a promising treatment for genetic diseases like β-thalassemia. Editing γ-globin promoters to disrupt ZBTB7A/LRF or BCL11A binding sites has shown potential for reactivating fetal hemoglobin and treating sickle cell disease. However, its application to β0-thalassemia/HbE disease remains unclear. This study utilized CRISPR/Cas9 to disrupt these sites in mobilized CD34 + hematopoietic stem /progenitor cells from healthy donors and β0-thalassemia/HbE patients. The editing efficiency for the BCL11A site (75-92%) was higher than for the ZBTB7A/LRF site (57-60%). Both disruptions similarly increased fetal hemoglobin production in healthy donors (BCL11A 26.2 ± 1.4%, ZBTB7A/LRF 27.9 ± 1.5%) and β0-thalassemia/HbE cells (BCL11A 62.7 ± 0.9%, ZBTB7A/LRF 64.0 ± 1.6%). Off-target effects were absent in BCL11A-edited cells but observed at low frequencies in ZBTB7A/LRF-edited cells. Neither disruption significantly affected erythroid differentiation. These findings highlight the comparable contributions of ZBTB7A/LRF and BCL11A binding sites to γ-globin reactivation. CRISPR/Cas9 editing of either site may offer a potential therapeutic strategy for β0-thalassemia/HbE disease.
    Keywords:   BCL11A ; ZBTB7A/LRF ; CRISPR/Cas9 genome editing; Fetal hemoglobin reactivation; β0-thalassemia/HbE; γ-globin promoter
    DOI:  https://doi.org/10.1038/s41598-025-10791-8
  3. Int J Mol Sci. 2025 Jun 30. pii: 6342. [Epub ahead of print]26(13):
    Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.
    Ninos Ioannis Vasiloudis, Kiriaki Paschoudi, Christina Beta, Grigorios Georgolopoulos, Nikoletta Psatha.
      Erythropoiesis, the process driving the differentiation of hematopoietic stem and progenitor cells to mature erythrocytes, unfolds through tightly orchestrated developmental stages, each defined by profound epigenetic remodeling. From the initial commitment of hematopoietic progenitors to the terminal enucleation of erythrocytes, dynamic changes in chromatin accessibility, transcription factor occupancy, and three-dimensional genome architecture govern lineage specification and stage-specific gene expression. Advances in our understanding of the regulatory genome have uncovered how non-coding elements, including enhancers, silencers, and insulators, shape the transcriptional landscape of erythroid cells. These elements work in concert with lineage-determining transcription factors to establish and maintain erythroid identity. Disruption of these epigenetic programs-whether by inherited mutations, somatic alterations, or environmental stress-can lead to a wide range of hematologic disorders. Importantly, this growing knowledge base has opened new therapeutic avenues, enabling the development of precision tools that target regulatory circuits to correct gene expression. These include epigenetic drugs, enhancer-targeted genome editing, and lineage-restricted gene therapies that leverage endogenous regulatory logic. As our understanding of erythroid epigenomics deepens, so too does our ability to design rational, cell-type-specific interventions for red blood cell disorders.
    Keywords:  chromatin remodeling; enhancer regulation; epigenetic therapy; erythropoiesis; hemoglobin switching; regulatory elements; transcription factors
    DOI:  https://doi.org/10.3390/ijms26136342
  4. J Clin Pathol. 2025 Jul 16. pii: jcp-2025-210055. [Epub ahead of print]
    Quantitative assessment of red blood cell surface molecules in hereditary spherocytosis.
    Tejashree Anil More, Prabhakar S Kedar.
       AIM: Hereditary spherocytosis (HS) refers to a heterogeneous disorder varying in genotypic and phenotypic features manifested by the production of spherocytes. The diseased cells can be eliminated from the circulatory system either by macrophages in the spleen in the extravascular pathway or the intravascular pathway via the complement cascade. This study aimed to investigate the status of red blood cell (RBC) surface molecules CD55 (decay accelerating factor), CD35 (complement receptor type 1-CR1), CD59 (MACIF), CD47 (marker of self) and CD71 (transferrin receptor) from individuals diagnosed with HS.
    METHODS: This study aims to quantitatively assess RBC surface molecules (CD35, CD55, CD59, CD47 and CD71) on peripheral RBCs from 42 HS patients and 30 healthy controls, carried out by flow cytometry using monoclonal antibodies.
    RESULTS: Our findings show that HS patients had a significant 58% decrease in anti-CD35 binding compared with healthy controls. This is the first study to demonstrate the presence of erythrocytes with reduced CD35 levels in HS patients. Compared with the control group, HS patients had comparable levels of CD59 and CD47, but their CD55 levels were significantly reduced, with a 30% decrease in anti-CD55 binding. The expression level of CD71 was higher in HS patients (3.33%) compared with healthy controls in our study.
    CONCLUSION: The diminished levels of CD35 and CD55 in HS patients may influence RBC clearance, possibly through mechanisms that remain fully understood and require further investigation, including their potential role in haemolytic crises. Further research employing molecular techniques is required to clarify their exact role in HS.
    Keywords:  Anemia, Hemolytic; Complement System Proteins; FLOW CYTOMETRY
    DOI:  https://doi.org/10.1136/jcp-2025-210055
  5. PLoS One. 2025 ;20(7): e0327132
    Case-control study of maternal and fetal outcomes in beta thalassaemia trait during pregnancy.
    Shyamali Thilakarathne, Udayanga P Jayaweera, Sanjaya Uduweralla, Sudath Pathinisekara, Thushari U Herath, Anuja Premawardhena.
      Individuals with beta thalassaemia trait are not expected to have clinically significant morbidities besides mild anaemia. Pregnancy would exaggerate the anaemia in beta thalassaemia traits, but how this could affect maternal and fetal outcomes is unclear. Previous studies on maternal and fetal outcomes in beta thalassaemia trait have been inconsistent and even contradictory. Thus, we aimed to study the outcomes of pregnancy in pregnant women with beta-thalassemia trait. The prospective case-control study included 120 pregnant women with beta thalassaemia trait and 120 normal pregnant women. Participants in the case and control groups were matched according to maternal age, gestational age and number of previous pregnancies. All participants were followed up at similar intervals for the duration of the pregnancy for haemoglobin variations, transfusion requirements and maternal/fetal problems without interfering with the management. We identified that beta thalassaemia traits did not experience noteworthy symptoms in any of the three trimesters: except for headache. Haemoglobin level, and red cell indices in all three trimesters were significantly lower among cases than controls. In both groups hemoglobin levels dipped in the 2nd trimester, only to rise in the 3rd trimester, to reach values similar to those in the 1st trimester. Individuals with beta thalassaemia trait were transfused more blood during the 2nd and 3rd trimesters based on lower Hb levels of the mother a decision not prompted by any notable maternal or fetal complications. No statistically significant differences were observed for pregnancy complications, perinatal or neonatal outcomes. During labor, the rate of caesarean deliveries was significantly higher among cases with no definite indications for such in most cases.
    DOI:  https://doi.org/10.1371/journal.pone.0327132
  6. Clin Appl Thromb Hemost. 2025 Jan-Dec;31:31 10760296251359291
    Coagulation and Fibrinolysis Dysregulation in β-Thalassemia Major: Potential Impact of Splenectomy and Medications on Thrombotic Risk.
    Ola M Al-Sanabra, Manal A Abbas, Wafà J Hazà, Abeer A Hazàa, Ahmad K Al Tibi.
      ObjectiveThe dysregulation of clotting factors in β-thalassemia major is not fully understood. This case-control study examines the impact of splenectomy and medications on clotting factor dysregulation.MethodsLab. tests of coagulation and fibrinolysis were performed.ResultsThis study included 60 β-thalassemia major patients of both sexes (7-35 years) and 20 age-matched controls. None of the participants had a previous thrombotic event. No difference existed between control and β-thalassemia groups in all tested parameters except for protein S (PS) which was 26.1% lower in β-thalassemia group compared to the control group (p = 0.0001) while D-Dimer, plasminogen activator inhibitor-1 (PAI-1) and platelet count showed an increase in their levels by 53.6%, 93.4% and 112.7%, respectively compared to the control (p = 0.004, p = 0.0001, p = 0.0001, respectively). Notably, a strong positive correlation existed between platelet count and PAI-1 (r = 0.669, p = 0.0001) in β-thalassemia group. Splenectomized patients had higher platelet count (+45.2%), PAI-1 (+98.1%), fibrinogen (+18.9%) and tPA (+197.2%) compared to the non-splenectomized group (all p < 0.05). No significant differences in PS, D-dimer, PT, INR, aPTT, fibrinogen, PC, TF, tPA or ADAMTS13 were found between β-thalassemia major patients taking and not taking aspirin. However, a higher platelet count (+37.1%) and PAI-1 level (+58.9%), along with a lower vWF level (-25.6%), were observed between these two groups (all p < 0.05).ConclusionElevation in PAI-1 and platelet count in splenectomized β-thalassemia major could increase the risk of having a thrombotic event. Medications may have significant interactions with blood coagulation in β-thalassemia.
    Keywords:  aspirin; iron-chelation; plasminogen activator inhibitor-1; protein s; splenectomy; β-thalassemia
    DOI:  https://doi.org/10.1177/10760296251359291
  7. EJHaem. 2025 Aug;6(4): e70077
    Morphologic and Electrophoretic Features of Hemoglobin Bart's Hydrops Fetalis.
    Ali Amid, Elona Turley, Nicholas Au, Audi Setiadi.
      
    Keywords:  alpha‐thalassemia; anemia; blood transfusion ‐ intrauterine; fetal hydrops
    DOI:  https://doi.org/10.1002/jha2.70077
  8. Nat Rev Drug Discov. 2025 Jul 14.
    CRISPR-based therapeutic genome editing for inherited blood disorders.
    Sébastien Levesque, Daniel E Bauer.
      Therapeutic genome editing promises to transform medicine. Pivotal discoveries have provided a diverse and versatile set of tools to correct pathogenic mutations or produce protective alleles using CRISPR-based technologies. These innovative therapies are especially adaptable for blood and immune disorders, where clinical methods allow haematopoietic stem cells (HSCs) to be mobilized, harvested, engineered ex vivo and transplanted back into a patient to permanently replace their blood system. This paradigm has been exemplified with the first US Food and Drug Administration (FDA)-approved CRISPR-Cas9 therapy for sickle cell disease and β-thalassaemia, exa-cel (Casgevy). Although promising, efficient delivery of gene edits involves complicated ex vivo manipulation and toxic myeloablative conditioning. The quiescent and elusive nature of HSCs also brings associated challenges. In this Review, we explore the state-of-the-art genome editing technologies of nucleases, base editors and prime editors, which hold promise to address unmet clinical needs for patients with inherited haematological disorders. We highlight the progress made for several disorders and discuss the challenges that remain for ex vivo and in vivo targeting of HSCs for next-generation gene therapies.
    DOI:  https://doi.org/10.1038/s41573-025-01236-y
This page is being maintained by Thomas Krichel. It was last updated on 2025‒08‒03 at 15:42.