Transcription-coupled repair - mechanisms of action, regulation, and associated human disorders.

The transcription-coupled repair (TCR) pathway resolves transcription-blocking DNA lesions to maintain cellular function and prevent transcriptional arrest. Stalled RNA polymerase II (RNAPII) triggers repair mechanisms, including RNAPII ubiquitination, which recruit UVSSA and TFIIH. Defects in TCR-associated genes cause disorders like Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and recently defined AMeDS.

Allogeneic Stem Cell Transplant in Hematological Disorders: A Decade of Experience.

: Allogeneic hematopoietic cell transplantation (allo-HCT) is a complex procedure with the potential to provide curative treatment for various hematological disorders. This study aims to evaluate the outcomes of allo-HCT in hematological diseases and identify significant complications in a single-center setting. : We conducted a retrospective analysis of 180 patients with hematological diseases who underwent allo-HCT between January 2011 and December 2021.

Diagnosis of Diamond-Blackfan anemia in adulthood: case series and review of the literature.

Diamond-Blackfan anemia (DBA) is a rare constitutional inherited bone marrow failure syndrome (iBMF) characterized by progressive severe non-regenerative anemia and congenital abnormalities. Diagnosis is made by identification of a DBA-causing variant, typically in a ribosomal protein gene. More than 99% of patients are diagnosed in the pediatric age, but clinical manifestation may be mild and severe anemia can occur later in the patient's life.

Parvovirus B19 infection in children: a comprehensive review of clinical manifestations and management.

Parvovirus B19 (B19V) is a significant pathogen responsible for a wide range of clinical manifestations, particularly in children and pregnant women. While B19V is most commonly recognized as the cause of Fifth disease, a mild erythematous illness in children, its clinical impact extends far beyond this condition. B19V can lead to severe complications, including transient aplastic crisis in individuals with chronic hemolytic anemias, arthralgia, and more severe joint diseases.

A rare case report of severe aplastic anaemia caused by long-term use of zidovudine.

Background: Zidovudine is an antiviral drug used to treat acquired immune deficiency syndrome (AIDS). Anaemia is a common adverse effect of zidovudine that usually occurs in the first 2 to 4 weeks of initial treatment. Here, we describe a patient with HIV infection who developed severe aplastic anaemia 11 years after taking zidovudine.

A potential predictive model based on machine learning and CPD parameters in elderly patients with aplastic anemia and myelodysplastic neoplasms.

Background: Aplastic anemia (AA) and myelodysplastic neoplasms (MDS) have similar peripheral blood manifestations and are clinically characterized by reduced hematological triad. It is challenging to distinguish and diagnose these two diseases. Hence, utilizing machine learning methods, we employed and validated an algorithm that used cell population data (CPD) parameters to diagnose AA and MDS.

Outpatient subcutaneous alemtuzumab is feasible and safe for aplastic anemia and associated with high response rates.

Immunosuppressive therapy (IST) using horse antithymocyte globulin (h-ATG) combined with cyclosporine (CsA) and eltrombopag is the standard care for aplastic anemia (AA) in patients without a suitable matched donor. However, in many countries, h-ATG use has been discontinued, leaving rabbit ATG (r-ATG), which has a lower response rates and poorer survival, as the only alternative. In previous studies, alemtuzumab (ALZ), a humanized monoclonal antibody targeting CD52, combined with CsA resulted in an adequate ORR in AA patients.

Classification and Prognostic Stratification Based on Genomic Features in Myelodysplastic and Myeloproliferative Neoplasm- and Their Overlapping Conditions.

: Myeloid neoplasms encompass a diverse group of disorders. In this study, we aimed to analyze the clinical and genomic data of patients with myeloproliferative neoplasm (MPN), myelodysplastic neoplasm (MDS), and their overlapping conditions, such as MDS/MPN and aplastic anemia (AA), to help redefine the disease classification. : Clinico-genomic data of 1585 patients diagnosed with MPN ( = 715), MDS ( = 698), MDS/MPN ( = 78), and AA ( = 94) were collected.

Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, non-malignant hematologic disease characterized by complement-mediated hemolysis (with or without hemoglobinuria), fatigue, increased susceptibility to thrombosis, and bone marrow dysfunction. The development of complement inhibitors has transformed outcomes for patients with PNH, but patients may still experience pharmacodynamic breakthrough hemolysis (BTH), which can be caused by exposure to a complement amplifying condition (CAC), such as vaccination, infection, or surgery.

Materials And Methods: A 13-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on how to classify pharmacodynamic BTH in patients with complement-inhibitor treated PNH.

Aplastic Anemia: Demographic and Clinical Characteristics in Costa Rica.

Background Aplastic anemia (AA) is a rare and heterogeneous hematological disorder defined as pancytopenia with hypocellular bone marrow in the absence of abnormal infiltration or medullary fibrosis. Various causes of AA have been identified, such as autoimmune factors, bone marrow injuries, viral infections, and genetic disorders. The symptoms of AA are directly linked to pancytopenia and the most common are fatigue, recurrent infections, and bleeding problems.

Similar outcomes between HLA-haploid and matched sibling donor hematopoietic stem cell transplantation: a multicenter, retrospective study and severe aplastic anemia transplant-specific prognostic scoring system.

In recent years, great progress has been made in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) treatment for hematological malignant diseases because of the advent of novel conditioning regimens, optimized graft manipulation, improved graft-versus-host disease (GVHD) prophylaxis, and advances in supportive care. Recent studies have shown very favorable outcomes in severe aplastic anemia (SAA) patients, with comparable outcomes to those of patients receiving immune suppressive therapy (IST) and allogeneic HSCT from a matched sibling donor (MSD) or matched unrelated donor (MUD). However, most of the previous studies relied on single-center data analyses, and the conditioning regimen, GVHD prophylaxis and supportive care used were relatively singular.

Etiological Spectrum of Bone Marrow Biopsy in Patients With Pancytopenia.

Background Pancytopenia is defined as a decrease in all three hematologic cell lines. The condition is not a disease in itself but a common pathway caused by various etiologies that can be infectious, autoimmune, genetic, nutritional, and/or malignant. Determining the cause of pancytopenia is a challenge and is key in determining the proper treatment regimen and estimating prognosis.

Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling.

Background: Distinguishing donor- vs. recipient-derived myelodysplastic neoplasm (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is challenging and has direct therapeutical implications.

Methods: Here, we took a translational approach that we used in addition to conventional diagnostic techniques to resolve the origin of MDS in a 38-year-old patient with acquired aplastic anemia and evolving MDS after first allo-HSCT.

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

Dynamic tracking of native precursors in adult mice.

Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors.

BRAF inhibitors enhance erythropoiesis and treat anemia through paradoxical activation of MAPK signaling.

Erythropoiesis is a crucial process in hematopoiesis, yet it remains highly susceptible to disruption by various diseases, which significantly contribute to the global challenges of anemia and blood shortages. Current treatments like erythropoietin (EPO) or glucocorticoids often fall short, especially for hereditary anemias such as Diamond-Blackfan anemia (DBA). To uncover new erythropoiesis-stimulating agents, we devised a screening system using primary human hematopoietic stem and progenitor cells (HSPCs).

Cord Blood Transplantation Using Myeloablative Conditioning for Pediatric Advanced Myelodysplastic Syndrome in AMeD Syndrome With a Novel ADH5 Variant.

Aplastic anemia, mental retardation, and dwarfism syndrome (AMeDS) is a rare inherited bone marrow failure syndrome. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only possible treatment option for hematological complications in AMeDS; however, there are no reports addressing allo-HSCT for AMeDS. A 6-year-old female diagnosed with AMeDS accompanying myelodysplastic syndrome with increased blast was successfully treated with cord blood transplantation followed by myeloablative conditioning (MAC).

A multicentre, retrospective study of epidemiology and outcome of aplastic anaemia among adult population in Sabah and Sarawak from year 2006 to 2017.

Introduction: Aplastic anaemia (AA) is a rare disorder of bone marrow failure, characterized by bone marrow hypocellularity with pancytopenia. The annual incidence rates of AA in Asia are observed to be two to three times higher than Europe and North America. Since the introduction of immunosuppressive therapy (IST) and of allogenic stem cell transplant (SCT), the outcome of severe AA has significantly improved.