bims-conane 2026-01-11 papers

J Clin Med. 2025 Dec 31. pii: 308. [Epub ahead of print]15(1):

Ineffective Erythropoiesis Markers in β-Thalassemia: A Systematic Review.

Kartika Prahasanti, Ami Ashariati, Lilik Herawati, Pradana Zaky Romadhon, Bagus Aulia Mahdi, Afifah Zahra Dzakiyah, Maulana Bagus Adi Cahyono, Narazah Mohd Yusoff.

Background/Objectives: Ineffective erythropoiesis (IE) is a hallmark of β-thalassemia and contributes to major clinical complications, including severe anemia, extramedullary hematopoiesis, and progressive iron overload. Despite its central role in disease pathophysiology, there is no established biomarker for the reliable identification and monitoring of IE. This systematic review was conducted to evaluate potential serum markers that reflect IE in β-thalassemia. Methods: Across seven databases (PubMed, ScienceDirect, Web of Science, SpringerLink, Taylor & Francis, ProQuest, and SAGE), thirteen studies met the eligibility criteria and were analyzed to identify circulating biomarkers associated with IE in β-thalassemia. Results: The most consistently reported markers were growth differentiation factor-15 (GDF-15), soluble transferrin receptor (sTfR), erythropoietin (EPO), and erythroferrone (ERFE), all of which demonstrated strong correlations with the degree of IE and erythroid expansion. Additional markers, including circulating cell-free DNA (cfDNA), CA15.3, hepcidin, ferritin, and phosphatidylserine (PS)-exposed red blood cells, were also found to be elevated, reflecting increased erythroid turnover, apoptosis, and secondary iron dysregulation. These findings suggest that while individual markers capture different aspects of IE, their combined evaluation may provide a more comprehensive picture of disease burden. Conclusions: IE represents the central pathophysiological driver of β-thalassemia and is closely linked to disease complications. Early detection through circulating biomarkers offers the potential for timely identification of high-risk patients, monitoring of therapeutic responses, and prognostication. Although current evidence highlights GDF-15, sTfR, ERFE, and EPO as the most promising candidates, further validation in larger, longitudinal cohorts is required before clinical implementation.

Keywords: anemia; ineffective erythropoiesis; iron overload; marker; thalassemia

DOI: https://doi.org/10.3390/jcm15010308

EMBO Mol Med. 2026 Jan 09.

TKI-mediated inhibition of NLRP1 inflammasome restores erythropoiesis in DBA syndrome.

Diamond-Blackfan anemia syndrome (DBAS) is marked by defective erythropoiesis caused by impaired ribosome biogenesis and aberrant signaling. Here, we investigate how ribosomal stress-induced activation of the NLRP1 inflammasome affects erythroid differentiation in DBAS. We demonstrate that FDA/EMA-approved tyrosine kinase inhibitors (TKIs) effectively mitigate defective erythropoiesis by inhibiting NLRP1 inflammasome activation. In K562 cells, nilotinib suppresses the ZAKα/P38/NLRP1/CASP1 axis, leading to increased GATA1 levels and upregulation of key erythroid genes. These effects were validated in human CD34⁺ hematopoietic stem and progenitor cells (HSPCs) and zebrafish models, where nilotinib, imatinib, and dasatinib promoted erythropoiesis while reducing caspase-1 activity. In Rps19-deficient zebrafish, RPS19-deficient human HSPCs, and HSPCs from DBAS patients, TKIs rescued erythroid differentiation and restored hemoglobin levels. Our findings highlight that targeting the NLRP1 inflammasome with TKIs may provide a novel therapeutic strategy for DBAS and other ribosomopathies.

Keywords: Diamond-Blackfan Anemia Syndrome; Drug Repurposing; NLRP1; Tyrosine Kinase Inhibitors; Zebrafish

DOI: https://doi.org/10.1038/s44321-025-00368-3

Am J Hematol. 2026 Jan 08.

Mechanistic Consequences of Piezo1 Gain-of-Function Variants for Decreased Red Cell Survival in Hereditary Xerocytosis.

Asya Makhro, Rick Huisjes, Elena Seiler, Min Qiao, Marije Bartels, Inga Hegemann, Patrick Eppenberger, Nicole Bender, Isabel Dorn, Anna Bogdanova, Richard van Wijk, Lars Kaestner.

DOI: https://doi.org/10.1002/ajh.70188

Cureus. 2025 Dec;17(12): e98434

Hereditary Persistence of Fetal Hemoglobin Presenting With 100% Fetal Hemoglobin and Recurrent Thrombotic Events.

Garry G Lachhar, Salman Syed, Ali Abdullah, Alexandros Konstantinidis, Stephen Pentheros, Alfredo Torres.

Fetal hemoglobin (HbF) is the predominant hemoglobin during fetal development, typically replaced by adult hemoglobin after birth. Elevated HbF levels in adulthood are rare and often associated with genetic conditions such as hereditary persistence of fetal hemoglobin (HPFH) or hemoglobinopathies. We present the case of a 30-year-old Pakistani male with 100% HbF, recurrent thrombotic events, including splenic thrombosis and unprovoked pulmonary embolism, and chronic systemic symptoms. Despite extensive evaluation, including bone marrow biopsy, advanced imaging, and multidisciplinary consultations, establishing a definitive diagnosis remained challenging. Genetic testing revealed a homozygous Asian-Indian deletion-inversion in the β-globin cluster. The patient's clinical course was complicated by persistent leukocytosis and compensated hemolysis. To our knowledge, this represents the first reported case in the literature of an adult with 100% HbF presenting with recurrent thrombotic complications. This case highlights the diagnostic complexity of rare hematological conditions and the potential association between 100% HbF and thrombotic complications, challenging the traditional view of HPFH as a benign condition.

Keywords: asian-indian deletion-inversion; beta-globin gene; fetal hemoglobin; hereditary persistence of fetal hemoglobin; thrombosis

DOI: https://doi.org/10.7759/cureus.98434

Am J Hematol. 2026 Jan 07.

Hematologic Landscape of Adult Patients With Diamond-Blackfan Anemia Syndrome.

Information about Diamond-Blackfan anemia syndrome (DBAS), a ribosomopathy associated with anemia, congenital anomalies and cancer predisposition is limited in adults. Using the French DBAS registry, 235 adult patients with DBAS were analyzed for hematological outcomes. At last follow-up, anemia, neutropenia, thrombocytopenia, and pancytopenia affected respectively 78%, 31%, 15%, and 11% of the patients. There was no severe aplastic anemia outside of clonal evolution. Among patients without DBAS-specific treatment (e.g., steroids or red blood cell transfusions), the incidence of anemia, neutropenia, and thrombocytopenia was 52%, 35%, and 10%, highlighting that treatment independence does not mean hematologic remission. Four patients developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), all associated with poor-risk features and dismal outcomes. Observed to expected ratios were 155 for MDS and 55.4 for AML, confirming a major risk-excess despite stringent criteria for MDS diagnosis. With a median follow-up of 32.2 years (IQR 26-44), overall survival (OS) was 98.0% (95% CI, 95.8-100), 90.6% (95% CI, 84.2-97.5), and 70.7% (95% CI, 57.3-87.2) at 30, 40, and 50 years respectively. Solid and hematologic cancers were the main cause of death. This study demonstrates, in a large cohort of adults with DBAS, that cytopenias beyond anemia are frequent and persistent. Myeloid neoplasms occur with a high incidence and dismal outcomes. These findings highlight the need for risk stratification, tailored surveillance, and optimized therapeutic strategies in this vulnerable population.

DOI: https://doi.org/10.1002/ajh.70197