Under steady state conditions, humans must produce ∼2 million red blood cells per second to sustain normal red blood cell counts and hemoglobin levels. Ineffective erythropoiesis, also termed dyserythropoiesis, is a process by which erythroid precursors die or fail to efficiently differentiate in the bone marrow. Ineffective erythropoiesis is characterized by expanded bone marrow erythropoiesis and increased erythroferrone production by bone marrow erythroblasts, with the latter resulting in reduced hepcidin production and increased iron absorption. Ineffective erythropoiesis may result from acquired and congenital conditions. Inherited causes of ineffective erythropoiesis include β-thalassemia, sideroblastic anemias, pyruvate kinase deficiency, and congenital dyserythropoietic anemias. This manuscript reviews the definition and evidence for ineffective erythropoiesis and describes the most common hereditary disorders of dyserythropoiesis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884990 | PMC |
http://dx.doi.org/10.1016/j.bcmd.2025.102910 | DOI Listing |
Am J Hematol
March 2025
Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero- Universitaria Careggi, University of Florence, Florence, Italy.
Myelofibrosis (MF) is a myeloproliferative neoplasm that is accompanied by driver JAK2, CALR, or MPL mutations in more than 90% of cases, leading to constitutive activation of the JAK-STAT pathway. MF is a multifaceted disease characterized by trilineage myeloid proliferation with prominent megakaryocyte atypia and bone marrow fibrosis, as well as splenomegaly, constitutional symptoms, ineffective erythropoiesis, extramedullary hematopoiesis, and a risk of leukemic progression and shortened survival. Therapy can range from observation alone in lower-risk and asymptomatic patients to allogeneic hematopoietic stem cell transplantation, which is the only potentially curative treatment capable of prolonging survival, although burdened by significant morbidity and mortality.
View Article and Find Full Text PDFAm J Hematol
March 2025
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Anemia in myeloid neoplasms is multifaceted, with heterogeneous pathogenetic mechanisms that include ineffective erythropoiesis, hepcidin-induced iron-restricted erythropoiesis, and abnormal inflammatory cytokine production. Current management of anemia is challenged by limited approved drugs that specifically treat anemia in myelofibrosis (MF) and myelodysplastic syndrome (MDS). Newer therapies target the transforming growth factor beta (TGF-β)-bone morphogenic protein/sons of mothers against decapentaplegic (BMP-SMAD) signaling pathway, which plays a significant role in ineffective erythropoiesis (SMAD 2/3) and abnormal hepcidin production (SMAD 1/5/8).
View Article and Find Full Text PDFAnn Hematol
March 2025
Department of Pediatrics: Immuno-Hematology and Stem Cell Transplantation, Bone Marrow Transplantation Center, Rue Djebel Lakhdhar, 1006, Tunis, Tunisia.
Sideroblastic anemias (SAs) represent a heterogeneous group of rare hematological disorders characterized by iron accumulation in mitochondria of erythroblasts with ineffective erythropoiesis. SAs are categorized into acquired and congenital forms. Acquired, secondary, and clonal, SA is rare in pediatric populations.
View Article and Find Full Text PDFHemoglobin
March 2025
Division of Pediatric Hematology/Oncology, University of California San Francisco, San Francisco, California, USA.
Alpha thalassemia major (ATM) is the most severe form of α-thalassemia, with thousands of cases annually throughout the world. It was historically incompatible with life, with almost all affected individuals dying at or before birth. Recent advances utilizing early, serial intrauterine transfusions have resulted in improved outcomes, including improved neurocognitive functioning and less congenital anomalies.
View Article and Find Full Text PDFJ Clin Med
February 2025
SC di Medicina ad Indirizzo Metabolico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milano, Italy.
The inherited genetic disorder β-thalassemia affects the hematopoietic system and is caused by the low production or absence of adult hemoglobin (HbA). Ineffective erythropoiesis is the hallmark of β-thalassemia pathophysiology and is characterized by an erythropoietin-driven substantial increase in erythroblast proliferation, coupled with an increase in late-stage precursor apoptosis, which results in low levels of circulating mature red blood cells (RBCs) and chronic anemia. Mitochondrial dysfunction commonly occurs in these cells because of the increased demand for energy production and the need to manage abnormal hemoglobin chain synthesis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!