Bone marrow failure syndromes comprise a heterogeneous group of disorders characterized by impaired hematopoiesis, peripheral blood cytopenias, and variable risks of clonal evolution and malignant transformation. Advances in molecular genetics and next-generation sequencing have improved understanding of the mechanisms underlying inherited bone marrow failure syndromes (IBMFS) and acquired aplastic anaemia (AA). Although these disorders arise from distinct pathogenic mechanisms, they share common pathways involving hematopoietic stem cell dysfunction, clonal selection, and predisposition to myelodysplastic neoplasms (MDS) and acute myeloid leukaemia (AML). This review discusses the molecular basis of major IBMFS, including Fanconi anaemia, dyskeratosis congenita, severe congenital neutropenia, Diamond–Blackfan anaemia, Shwachman–Diamond syndrome, congenital amegakaryocytic thrombocytopenia, and thrombocytopenia with absent radius, emphasizing the mechanisms driving clonal evolution. Defective DNA repair, telomere dysfunction, ribosomal stress, and sustained proliferative pressure can compromise stem-cell fitness and promote adaptive or preleukemic clones. In acquired AA, immune-mediated stem-cell destruction creates selective pressure favouring clones with survival advantages. Somatic mutations involving PIGA, BCOR, BCORL1, DNMT3A, and ASXL1 demonstrate heterogeneous clinical behaviour, with some associated with favourable responses to immunosuppressive therapy and others with increased risks of progression to MDS or AML. Integrating clinical assessment, cytogenetic analysis, flow cytometry, and molecular profiling is essential for diagnosis, risk stratification, and longitudinal surveillance. Understanding clonal evolution across inherited and acquired bone marrow failure syndromes provides a framework for individualized monitoring and therapeutic decision-making, including consideration of allogeneic hematopoietic stem cell transplantation.
Hemoglobin J (Hb J) comprises a heterogeneous group of structural hemoglobin variants that are generally clinically silent. We describe a familial occurrence identified in four members following repeated failure of HbA1c estimation. Subsequent HPLC demonstrated a prominent P3 fraction (25.2–26.6
Sickle cell disease (SCD) remains a major health burden in India, disproportionately affecting tribal populations living in rural and resource-limited settings. Despite the availability of confirmatory laboratory methods for sickle cell testing, access is limited in rural regions resulting in many avoidable health complications. This demands the need for developing and validating new point-of-care testing (POCT) solutions for SCD that is low-cost and easy to operate. In this regard, this study aimed to evaluate the SCD diagnostic performance of in-house developed optical absorbance-based sickle-solubility testing (OST) kit and its analyzer in comparison to reference standard high-performance liquid chromatography (HPLC) method. The study included 1,024 de-identified left-over blood samples (466 positives, 558 negatives) used for HPLC-based sickle hemoglobin (HbS) percentage determination. The samples were tested using OST and the results were compared with HPLC findings for determination of diagnostic performance of OST. OST analysis for SCD detection in comparison with HPLC demonstrated a sensitivity, specificity and overall accuracy of 96.14
