Bone marrow failure
Conditions
Interventions
Patients with acquired bone marrow failure syndromes:None
Healthy Control:None
Sponsors
Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients with acquired bone marrow failure syndromes: (1) Diagnosis meeting internationally recognized criteria for acquired bone marrow failure syndromes: Aplastic anemia (AA): According to the revised Camitta criteria. Paroxysmal nocturnal hemoglobinuria (PNH): According to the International PNH Interest Group criteria. Myelodysplastic syndrome (MDS): According to the WHO classification (5th edition) criteria. Immuno-related hemocytopenia/pancytopenia (IRH/IRP): Preliminary diagnostic criteria: cytopenia involving one, two, or three lineages in peripheral blood, with reticulocyte count and/or neutrophil percentage not decreased; bone marrow shows no decrease in erythroid or granulocytic lineage percentages, or normal megakaryocyte count, often with erythroid hematopoietic islands or hemophagocytosis; other primary or secondary causes of cytopenia have been excluded. Confirmed diagnostic criteria: Meeting the preliminary criteria, or detection of membrane-bound autoantibodies on bone marrow hematopoietic cells (diagnosis confirmed before treatment), or absence of such autoantibodies but confirmed by effective treatment with adequate corticosteroids, and/or high-dose intravenous immunoglobulin, and/or CD20 monoclonal antibody therapy (diagnosis confirmed after treatment, with independence from blood component transfusion and varying degrees of recovery in one, two, or three blood cell lineages). (2) Hb < 100 g/L, excluding the influence of non-hematological conditions such as blood loss or chronic renal insufficiency. (3) Age 18–75 years. (4) Patients understand the study purpose and voluntarily provide written informed consent. 2. Healthy control: (1) No history of any known hematological diseases, autoimmune diseases, malignant tumors, or chronic infections. (2) All parameters of the complete blood count (including white blood cell count and differential, hemoglobin, platelet count, and reticulocyte count) are within the laboratory's normal reference ranges prior to sampling. (3) The control group is matched to the patient group in terms of age (+/-5 years) and sex distribution. (4) Healthy volunteers understand the study purpose and voluntarily provide written informed consent.
Exclusion criteria
Exclusion criteria: 1. Patients with Acquired Bone Marrow Failure Syndrome: (1)Congenital bone marrow failure syndrome, such as Fanconi anemia, dyskeratosis congenita, etc. (2)Bone marrow failure secondary to other definite etiologies, including: hematopoietic cell tumors; infiltration of the bone marrow by tumors from other systems; myelofibrosis; severe nutritional anemia; acute hematopoietic arrest; bone marrow suppression caused by radiotherapy or chemotherapy for neoplastic diseases, etc. (3)Patients with classic hemolytic PNH with a large clone size (e.g., >50%) and no clear evidence of bone marrow failure. (4)Received immunosuppressive therapies such as anti-thymocyte globulin or alemtuzumab within 3 months prior to enrollment. (5)Received hematopoietic-stimulating medications such as granulocyte colony-stimulating factor, erythropoietin, or thrombopoietin receptor agonists within 1 month prior to enrollment. (6)Received demethylating agents (e.g., decitabine, azacitidine) or immunomodulators within 3 months prior to enrollment. (7)Underwent allogeneic hematopoietic stem cell transplantation within 6 months prior to enrollment. (8)Uncontrolled active bacterial, fungal, or viral infections. (9)Decompensated cardiac, hepatic, or renal insufficiency. (10)Active solid tumors or other major diseases requiring active treatment. 2. Healthy Control Subjects:(1)Any abnormalities in hematological indicators, including but not limited to anemia, blood cell reduction, or blood cell proliferation. (2)Potential inflammatory or infectious conditions: history of acute infection, fever, or unexplained elevation of inflammatory markers such as C-reactive protein/erythrocyte sedimentation rate within 4 weeks prior to enrollment. (3)Special physiological or lifestyle conditions: pregnant or breastfeeding women; long-term heavy smoking (e.g., >10 cigarettes per day) or history of alcohol abuse; history of vaccination within 4 weeks. (4)Long-term medication use: regular use of drugs that may affect hematopoietic or immune function, such as corticosteroids, immunosuppressants, or non-steroidal anti-inflammatory drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DNA Methylation Level (e.g., Average Methylation Level, Differentially Methylated Regions DMRs);Histone Modification Status (e.g., H3K4me3, H3K27ac, H3K9me2, H3K27me3);Chromatin Accessibility (e.g., Changes in Enhancer and Promoter Accessibility);Three-Dimensional Genome Interactions (e.g., Chromatin Looping at ß-Globin Gene Cluster and Topologically Associating Domain TAD Structure);Cell Proliferation and Viability;Cell Apoptosis Rate;Erythroid Differentiation Efficiency (BFU-E and CFU-E Colony Formation; Expression of Erythroid Markers CD71 and CD235a);Total Hemoglobin Content;Fetal Hemoglobin (HbF) Expression Level (?-Globin); | — |
Secondary
| Measure | Time frame |
|---|---|
| Differentially Expressed Epigenetic Regulatory Factors (e.g., LSD1, BRD2/4);Construction of Epigenetic Regulatory Networks (Co-expression Network, Protein-Protein Interaction Network, Core Hub Genes);Correlation Between Expression Levels or Activities of Key Epigenetic Factors and Erythroid Differentiation Capacity, Hemoglobin Production Levels;Targeted Activity Changes of LSD1 (H3K4me2/3 Levels) and BET Proteins (BRD4 Chromatin Dissociation);Downstream Gene Expression Regulation (Key Erythroid Differentiation Genes GATA1, TAL1, ?/ß-Globin);Histone Modification (H3K4me2/3) and Chromatin Accessibility Changes at Specific Genomic Loci (e.g., ?-Globin Promoter);Activity of Erythroid-Related Signaling Pathways (e.g., TGF-ß/Smad, JAK/STAT); | — |
Countries
China
Contacts
Public ContactGong Yuemin
Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
Outcome results
None listed