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Acquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1K700E. SF3B1K700E expressing cells showed higher proportion of RS than the control cells along with erythroid differentiation, indicating the direct contribution of mutant SF3B1 expression in erythroblasts to RS formation. In SF3B1K700E expressing cells, ABCB7 and ALAS2, known causative genes for congenital sideroblastic anemia, were downregulated. Additionally, mis-splicing of ABCB7 was observed in SF3B1K700E expressing cells. ABCB7-knockdown HUDEP-2 cells revealed an increased frequency of RS formation along with erythroid differentiation, demonstrating the direct molecular link between ABCB7 defects and RS formation. ALAS2 protein levels were obviously decreased in ABCB7-knockdown cells, indicating decreased ALAS2 translation owing to impaired Fe–S cluster export by ABCB7 defects. Finally, RNA-seq analysis of MDS clinical samples demonstrated decreased expression of ABCB7 by the SF3B1 mutation. Our findings contribute to the elucidation of the complex mechanisms of RS formation in MDS-RS. [ABSTRACT FROM AUTHOR]

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive lymphoid malignancy, frequently involving the central nervous system (CNS). However, exclusive CNS infiltration of T-ALL without leukemic presentation at initial diagnosis is extremely rare. Herein, we report the case of a 19-year-old male patient who presented with progressively worsening head and neck pain, dysphagia, and dizziness. No leukemic cells were detected in peripheral blood or bone marrow samples. Computed tomography revealed only a small anterior mediastinal mass and mildly high density in some areas of the bone marrow. Although brain magnetic resonance imaging (MRI) showed no abnormal findings, spine MRI revealed slight contrast enhancement of the cauda equina. A spinal tap revealed massive infiltration of abnormal lymphoid cells that were diagnosed as T-ALL/LBL based on morphological and immunophenotypic findings. Urgent intravenous and intrathecal chemotherapeutic intervention resulted in a rapid reduction in leukemic cells in the cerebrospinal fluid, with relief of symptoms. Since T-ALL/LBL usually exhibits leukocytosis associated with a high frequency of CNS involvement, this case is considered an exceptional presentation. Recognition of such a rare presentation of T-ALL/LBL, which mimics other neurological diseases such as meningoencephalitis and demyelinating diseases, is important to avoid delayed diagnosis and treatment that could result in early death or severe neurological sequelae. [ABSTRACT FROM AUTHOR]

X-linked sideroblastic anemia (XLSA), the most common form of congenital sideroblastic anemia, is caused by a germline mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. In XLSA, defective heme biosynthesis leads to ring sideroblast formation because of excess mitochondrial iron accumulation. In this study, we introduced ALAS2 missense mutations on human umbilical cord blood-derived erythroblasts; hereafter, we refer to them as XLSA clones. XLSA clones that differentiated into mature erythroblasts showed an increased frequency of ring sideroblast formation with impaired hemoglobin biosynthesis. The expression profiling revealed significant enrichment of genes involved in ferroptosis, which is a form of regulated cell death induced by iron accumulation and lipid peroxidation. Notably, treatment with erastin, a ferroptosis inducer, caused a higher proportion of cell death in XLSA clones. XLSA clones exhibited significantly higher levels of intracellular lipid peroxides and enhanced expression of BACH1, a regulator of iron metabolism and potential accelerator of ferroptosis. In XLSA clones, BACH1 repressed genes involved in iron metabolism and glutathione synthesis. Collectively, defective heme biosynthesis in XLSA clones could confer enhanced BACH1 expression, leading to increased susceptibility to ferroptosis. The results of our study provide important information for the development of novel therapeutic targets for XLSA. [ABSTRACT FROM AUTHOR]

Monoclonal rearrangements of the TCR- genes were detected. f Flow cytometry scattergram of the lymphoma cells showing negative expression of TCR- and TCR- In the present case of TCR-silent PTCL, CD3, CD4, and CD8 were concomitantly absent, suggesting that the lymphoma cells were derived from thymocytes that have yet to express TCR and CD3 [[2]]. Dear Editor, T-cell receptor (TCR) is associated with diverse antigen recognition in T-cells [[1]]. [Extracted from the article]

The article presents a case study of a 39-year-old man who had previously suffered from high-risk myelodysplastic syndrome (MDS) and received unrelated cord blood transplantation (CBT) from a mismatched female donor. He was found positive for varicella zoster virus (VZV) IgM and IgG on viral serological tests. Also Epstein-Barr virus (EBV) coinfection with VZV had triggered Hemophagocytic lymphohistiocytosis (HLH). It also suggests to monitor patients for signs of HLH for years after CBT.