3,662 results match your criteria Wiskott-Aldrich Syndrome

Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing.

Nat Commun 2022 Jun 25;13(1):3646. Epub 2022 Jun 25.

Department of Research Laboratories and Director of Center for Stem Cell and Cell Therapy, Instituto G. Gaslini Children Hospital Scientific Institute, 16147, Genova, Italy.

The diverse functions of WASP, the deficiency of which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These models recapitulated WAS phenotypes and revealed that WASP deficiency causes an upregulation of numerous RNA splicing factors and widespread altered splicing. Read More

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WASHC1 interacts with MCM2-7 complex to promote cell survival under replication stress.

Mol Biol Rep 2022 Jun 22. Epub 2022 Jun 22.

Laboratory of Protein Structure and Function, Institute of Medicine and Pharmacy, Qiqihar Medical University, 161006, Qiqihar, Heilongjiang, China.

Background: WASHC1 is a member of the Wiskott-Aldrich syndrome protein (WASP) family and is involved in endosomal protein sorting and trafficking through the generation of filamentous actin (F-actin) via activation of the Arp2/3 complex. There is increasing evidence that WASHC1 is present in the nucleus and nuclear WASHC1 plays important roles in regulating gene transcription, DNA repair as well as maintaining nuclear organization. However, the multi-faceted functions of nuclear WASHC1 still need to be clarified. Read More

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Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India.

Sci Rep 2022 Jun 21;12(1):10416. Epub 2022 Jun 21.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Inborn errors of immunity (IEI) are a heterogeneous group of monogenic disorders that include primary immunodeficiency's and other disorders affecting different aspects of the immune system. Next-Generation Sequencing (NGS) is an essential tool to diagnose IEI. We report our 3-year experience in setting up facilities for NGS for diagnosis of IEI in Chandigarh, North India. Read More

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Targeting the WASF3 complex to suppress metastasis.

Pharmacol Res 2022 Jun 9;182:106302. Epub 2022 Jun 9.

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, 240W. Green St, Athens, GA 30602, United States. Electronic address:

Wiskott-Aldrich syndrome protein family members (WASF) regulate the dynamics of the actin cytoskeleton, which plays an instrumental role in cancer metastasis and invasion. WASF1/2/3 forms a hetero-pentameric complex with CYFIP1/2, NCKAP1/1 L, Abi1/2/3 and BRK1 called the WASF Regulatory Complex (WRC), which cooperatively regulates actin nucleation by WASF1/2/3. Activation of the WRC enables actin networking and provides the mechanical force required for the formation of lamellipodia and invadopodia. Read More

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WASP family proteins: Molecular mechanisms and implications in human disease.

Eur J Cell Biol 2022 Jun 1;101(3):151244. Epub 2022 Jun 1.

Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, 2437 Pammel Drive, Ames, IA 50011, USA. Electronic address:

Proteins of the Wiskott-Aldrich syndrome protein (WASP) family play a central role in regulating actin cytoskeletal dynamics in a wide range of cellular processes. Genetic mutations or misregulation of these proteins are tightly associated with many diseases. The WASP-family proteins act by transmitting various upstream signals to their conserved WH2-Central-Acidic (WCA) peptide sequence at the C-terminus, which in turn binds to the Arp2/3 complex to stimulate the formation of branched actin networks at membranes. Read More

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Structure of Arp2/3 complex at a branched actin filament junction resolved by single-particle cryo-electron microscopy.

Proc Natl Acad Sci U S A 2022 May 27;119(22):e2202723119. Epub 2022 May 27.

Department of Chemistry and Biochemistry and Institute of Molecular Biology, University of Oregon, Eugene, OR 97403.

SignificanceActin filament nucleation by Arp2/3 complex must be triggered by activators like WASP family proteins. Understanding how WASP proteins activate Arp2/3 complex has been a major challenge due to a lack of high-resolution structures of the complex in an activated state. We determined a high-resolution (∼3. Read More

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Inositol hexakisphosphate primes syndapin I/PACSIN 1 activation in endocytosis.

Cell Mol Life Sci 2022 May 9;79(6):286. Epub 2022 May 9.

The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, 171 76, Stockholm, Sweden.

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic β cells and that its knockdown abrogates β cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca channels. Intriguingly, inositol hexakisphosphate (InsP) activates casein kinase 2 (CK2) that phosphorylates syndapin I/PACSIN 1, thereby promoting interactions between syndapin I/PACSIN 1 and neural Wiskott-Aldrich syndrome protein (N-WASP) and driving β cell endocytosis. Read More

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Diagnosis and clinical management of Wiskott-Aldrich syndrome: current and emerging techniques.

Expert Rev Clin Immunol 2022 Jun 19;18(6):609-623. Epub 2022 May 19.

Division of Hematology Children's Hospital of Orange County, CA, USA.

Introduction: Wiskott-Aldrich syndrome (WAS) serves as the prototype of how variants in a gene, which encodes a protein central to actin cytoskeletal homeostasis can manifest clinically in a variety of ways including infection, atopy, autoimmunity, inflammation, bleeding, neutropenia, non-malignant lymphoproliferation, and malignancy. Despite the discovery of the gene almost 30 years ago, our understanding of the pathophysiological mechanisms underlying WAS continues to unfold.

Areas Covered: This review will provide an overview of the approach to the diagnosis of WAS as well as the management of its associated complications. Read More

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The Effects of Branched-Chain Amino Acids on the Akt/mTOR Pathway and Nebulin Protein in Joint Fixation-Induced Muscle Atrophy.

J Nutr Sci Vitaminol (Tokyo) 2022 ;68(2):112-119

Graduate School of Health Sciences, Kio University.

It is well known that branched-chain amino acids (BCAAs) promote protein synthesis in skeletal muscle and can cause muscle hypertrophy. However, it has also been reported that they may inhibit muscle atrophy induced by load-bearing and age-related changes. In this study, we investigated the effects of BCAA intake during joint fixation on the levels of protein kinase B (Akt), mammalian target of rapamycin (mTOR), and nebulin in a rat model of joint fixation. Read More

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Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.

Nat Cancer 2022 04 28;3(4):453-470. Epub 2022 Apr 28.

Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Phagocytosis is required for the optimal efficacy of many approved and promising therapeutic antibodies for various malignancies. However, the factors that determine the response to therapies that rely on phagocytosis remain largely elusive. Here, we demonstrate that mitochondrial fission in macrophages induced by multiple antibodies is essential for phagocytosis of live tumor cells. Read More

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Hypomethylation-mediated upregulation of the WASF2 promoter region correlates with poor clinical outcomes in hepatocellular carcinoma.

J Exp Clin Cancer Res 2022 Apr 28;41(1):158. Epub 2022 Apr 28.

Department of Gastroenterology, Ajou University School of Medicine, Worldcup-ro 164, Yeongtong-Gu, Suwon, 16499, Republic of Korea.

Background: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Wiskott-Aldrich syndrome protein family member 2 (WASF2) is an integral member of the actin cytoskeleton pathway, which plays a crucial role in cell motility. In this study, we aimed to explore the role of WASF2 in HCC carcinogenesis and its regulatory mechanism. Read More

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N-WASP Attenuates Cell Proliferation and Migration through ERK2-Dependent Enhanced Expression of TXNIP.

Biology (Basel) 2022 Apr 11;11(4). Epub 2022 Apr 11.

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.

Neural Wiskott-Aldrich Syndrome Protein (N-WASP) regulates actin cytoskeleton remodeling. It has been known that reduced N-WASP expression in breast and colorectal cancers is associated with poor prognosis. Here, we found reduced N-WASP expression in squamous cell carcinoma (SCC) patient samples. Read More

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Optimized Stapled Peptides Targeting WASF3 in Breast Cancer.

ACS Med Chem Lett 2022 Apr 8;13(4):570-576. Epub 2022 Mar 8.

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, United States.

Wiskott-Aldrich Syndrome Protein Family (WASF) members regulate actin cytoskeletal dynamics, and WASF3 is directly associated with breast cancer metastasis and invasion. WASF3 forms a heteropentameric complex with CYFIP, NCKAP, ABI, and BRK1, called the WASF Regulatory Complex (WRC), which cooperatively regulates actin nucleation by WASF3. Since aberrant deployment of the WRC is observed in cancer metastasis and invasion, its disruption provides a novel avenue for targeting motility in breast cancer cells. Read More

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Pharmacophore identification, virtual screening and activity verification of pedunsaponin A on target proteins PcAdv and PcnWAS of Pomacea canaliculata.

Pest Manag Sci 2022 Jul 6;78(7):3098-3107. Epub 2022 May 6.

College of Agronomy, Sichuan Agricultural University, Chengdu, China.

Target-protein-based pesticide screening has attracted wide-ranging attention on pesticide science. Pedunsaponin A (PA) is a compound isolated from the root of Pueraria peduncularis, and it has a strong toxic effect on Pomacea canaliculata. Previous studies found that Advlin (PcAdv) and neural Wiskott-Aldrich syndrome isoform X1(PcnWAS) are target proteins of PA when interacted with P. Read More

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Gene therapy for Whiskott-Aldrich syndrome: The latest news.

Clin Transl Med 2022 04;12(4):e815

Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.

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A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome.

Blood Adv 2022 Apr 11. Epub 2022 Apr 11.

University of Strasbourg, Strasbourg, France.

While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and absence of microthrombocytopenia. Only few XLN families have been reported so far and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. Read More

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The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.

Front Immunol 2022 16;13:799309. Epub 2022 Mar 16.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Actin is an important cytoskeletal protein involved in signal transduction, cell structure and motility. Actin regulators include actin-monomer-binding proteins, Wiskott-Aldrich syndrome (WAS) family of proteins, nucleation proteins, actin filament polymerases and severing proteins. This group of proteins regulate the dynamic changes in actin assembly/disassembly, thus playing an important role in cell motility, intracellular transport, cell division and other basic cellular activities. Read More

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WASF2 Serves as a Potential Biomarker and Therapeutic Target in Ovarian Cancer: A Pan-Cancer Analysis.

Front Oncol 2022 14;12:840038. Epub 2022 Mar 14.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Background: Wiskott-Aldrich syndrome protein family member 2 (WASF2) has been shown to play an important role in many types of cancer. Therefore, it is worthwhile to further study expression profile of WASF2 in human cancer, which provides new molecular clues about the pathogenesis of ovarian cancer.

Methods: We used a series of bioinformatics methods to comprehensively analyze the relationship between WASF2 and prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and tried to find the potential biological processes of WASF2 in ovarian cancer. Read More

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Lack of DOCK8 impairs the primary biologic functions of human NK cells and abrogates CCR7 surface expression in a WASP-independent manner.

Clin Immunol 2022 04 10;237:108974. Epub 2022 Mar 10.

Department of Molecular and Translational Medicine, University of Brescia, Italy.

Dedicator of Cytokinesis 8 (DOCK8) deficiency is a rare form of autosomal recessive combined immunodeficiency. The effect of DOCK8 deficiency on Natural Killer cell biology has not been fully elucidated yet. Thus, we undertook a detailed phenotypic and functional evaluation of NK cells from seven patients with DOCK8 deficiency. Read More

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IL-17-Dependent Dysregulated Cutaneous Immune Homeostasis in the Absence of the Wiskott-Aldrich Syndrome Protein.

Front Immunol 2022 21;13:817427. Epub 2022 Feb 21.

David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, Rochester, NY, United States.

Wiskott-Aldrich Syndrome (WAS) is characterized by recurrent infections, thrombocytopenia, and eczema. Here, we show that WASp-deficient mice on a BALB/c background have dysregulated cutaneous immune homeostasis with increased leukocyte accumulation in the skin, 1 week after birth. Increased cutaneous inflammation was associated with epithelial abnormalities, namely, altered keratinization, abnormal epidermal tight junctional morphology and increased trans-epidermal water loss; consistent with epidermal barrier dysfunction. Read More

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Critical role of WASp in germinal center tolerance through regulation of B cell apoptosis and diversification.

Cell Rep 2022 03;38(10):110474

Laboratory of Inherited Immune Disorders, Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

A main feature of Wiskott-Aldrich syndrome (WAS) is increased susceptibility to autoimmunity. A key contribution of B cells to development of these complications has been demonstrated through studies of samples from affected individuals and mouse models of the disease, but the role of the WAS protein (WASp) in controlling peripheral tolerance has not been specifically explored. Here we show that B cell responses remain T cell dependent in constitutive WASp-deficient mice, whereas selective WASp deletion in germinal center B cells (GCBs) is sufficient to induce broad development of self-reactive antibodies and kidney pathology, pointing to loss of germinal center tolerance as a primary cause leading to autoimmunity. Read More

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Atypical Wiskott-Aldrich syndrome without thrombocytopenia partially responding to omalizumab therapy.

Clin Exp Dermatol 2022 May 6;47(5):1013-1016. Epub 2022 Mar 6.

Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Primary immunodeficiencies with eczema can be easily misdiagnosed as atopic eczema, and thus require a high degree of awareness for diagnosis. Wiskott-Aldrich syndrome (WAS) is a rare disease and the fact that WAS without microthrombocytopenia has not been reported to date makes this case more interesting. As the patient's predominant problem was eczema and he had high circulating IgE antibodies in his serum, omalizumab was chosen as an appropriate steroid-sparing treatment option, as it has been shown to be effective in previous studies. Read More

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Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation.

Exp Mol Med 2022 Mar 4;54(3):226-238. Epub 2022 Mar 4.

Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Spain.

Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Read More

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An Autopsy Case of Wiskott-Aldrich Syndrome Revealing "FDC-Only Lymphoid Follicles" in Lymphoid Tissue: A Morphologic Correlate of Defective Immune Synapse.

Pediatr Dev Pathol 2022 May-Jun;25(3):345-350. Epub 2022 Mar 2.

Department of Hematology, RinggoldID:29751Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Wiskott-Aldrich Syndrome (WAS) is an inherited disorder characterized by the classical triad of eczema, micro-thrombocytopenia, and immune deficiency. This disease affects the hematopoietic cells to a variable extent. The spectrum of clinical and laboratory data for WAS has been well described in the literature though there is a paucity of its histopathologic and immunohistochemical correlates. Read More

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A lateral protrusion latticework connects neuroepithelial cells and is regulated during neurogenesis.

J Cell Sci 2022 03 30;135(6). Epub 2022 Mar 30.

Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Dynamic contacts between cells within the developing neuroepithelium are poorly understood but play important roles in cell and tissue morphology and cell signalling. Here, using live-cell imaging and electron microscopy we reveal multiple protrusive structures in neuroepithelial apical endfeet of the chick embryonic spinal cord, including sub-apical protrusions that extend laterally within the tissue, and observe similar structures in human neuroepithelium. We characterise the dynamics, shape and cytoskeleton of these lateral protrusions and distinguish them from cytonemes, filopodia and tunnelling nanotubes. Read More

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Wiskott-Aldrich syndrome: Oral findings and microbiota in children and review of the literature.

Clin Exp Dent Res 2022 02;8(1):28-36

Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.

Objective: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency, characterized by micro-thrombocytopenia, recurrent infections, and eczema. This study aims to describe common oral manifestations and evaluate oral microbioma of WAS patients.

Material And Methods: In this cohort study, 11 male WAS patients and 16 male healthy controls were evaluated in our Center between 2010 and 2018. Read More

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February 2022

Lymphocytes Utilize Somatic Mutations, Epigenetic Silencing, and the Proteasome to Escape Truncated WASP Expression.

J Clin Immunol 2022 May 12;42(4):753-759. Epub 2022 Feb 12.

Division of Immunology and Allergy, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Wiskott-Aldrich Syndrome Protein (WASP) deficiency causes Wiskott-Aldrich Syndrome (WAS), a sex-linked disorder characterized by combined immunodeficiency, microthrombocytopenia, and eczema. Like WASP-deficient humans, WASP-deficient mice produce normal numbers of functionally defective T cells. Here, we report a WAS patient with a novel germline frameshifting WAS mutation encoding a truncated form of WASP lacking the C-terminal cofilin homology (C) and the acidic region (A) domains (WASPΔCA). Read More

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Ex vivo observation of granulocyte activity during thrombus formation.

BMC Biol 2022 02 7;20(1):32. Epub 2022 Feb 7.

National Medical Research Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, 1 Samory Mashela St, Moscow, 117198, Russia.

Background: The process of thrombus formation is thought to involve interactions between platelets and leukocytes. Leukocyte incorporation into growing thrombi has been well established in vivo, and a number of properties of platelet-leukocyte interactions critical for thrombus formation have been characterized in vitro in thromboinflammatory settings and have clinical relevance. Leukocyte activity can be impaired in distinct hereditary and acquired disorders of immunological nature, among which is Wiskott-Aldrich Syndrome (WAS). Read More

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February 2022

WASp Deficiency Selectively Affects the TCR Diversity of Different Memory T Cell Subsets in WAS Chimeric Mice.

Front Immunol 2021 18;12:794795. Epub 2022 Jan 18.

National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.

Background: The T cell receptor (TCR) diversity is essential for effective T cell immunity. Previous studies showed that TCR diversity in Wiskott-Aldrich Syndrome (WAS) patients was severely impaired, especially in the memory T cell populations. Whether this defect was caused by intrinsic WASp deficiency or extrinsic reasons is still unclear. Read More

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February 2022

Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis.

Blood 2022 03;139(13):2066-2079

Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. Read More

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