Deciphering proteomic mechanisms explaining the role of glutathione as an aid in improving plant fitness and tolerance against cadmium-toxicity in Brassica napus L.

Cadmium (Cd) hazard is a serious limitation to plants, soils and environments. Cd-toxicity causes stunted growth, chlorosis, necrosis, and plant yield loss. Thus, ecofriendly strategies with understanding of molecular mechanisms of Cd-tolerance in plants is highly demandable. The Cd-toxicity caused plant growth retardation, leaf chlorosis and cellular damages, where the glutathione (GSH) enhanced plant fitness and Cd-toxicity in Brassica through Cd accumulation and antioxidant defense. A high-throughput proteome approach screened 4947 proteins, wherein 370 were differently abundant, 164 were upregulated and 206 were downregulated. These proteins involved in energy and carbohydrate metabolism, CO2 assimilation and photosynthesis, signal transduction and protein metabolism, antioxidant defense response, heavy metal detoxification, cytoskeleton and cell wall structure, and plant development in Brassica. Interestingly, several key proteins including glutathione S-transferase F9 (A0A078GBY1), ATP sulfurylase 2 (A0A078GW82), cystine lyase CORI3 (A0A078FC13), ferredoxin-dependent glutamate synthase 1 (A0A078HXC0), glutaredoxin-C5 (A0A078ILU9), glutaredoxin-C2 (A0A078HHH4) actively involved in antioxidant defense and sulfur assimilation-mediated Cd detoxification process confirmed by their interactome analyses. These candidate proteins shared common gene networks associated with plant fitness, Cd-detoxification and tolerance in Brassica. The proteome insights may encourage breeders for enhancing multi-omics assisted Cd-tolerance in Brassica, and GSH-mediated hazard free oil seed crop production for global food security.

Mutation order in acute myeloid leukemia identifies uncommon patterns of evolution and illuminates phenotypic heterogeneity.

Acute myeloid leukemia (AML) has a poor prognosis and a heterogeneous mutation landscape. Although common mutations are well-studied, little research has characterized how the sequence of mutations relates to clinical features. Using published, single-cell DNA sequencing data from three institutions, we compared clonal evolution patterns in AML to patient characteristics, disease phenotype, and outcomes. Mutation trees, which represent the order of select mutations, were created for 207 patients from targeted panel sequencing data using 1 639 162 cells, 823 mutations, and 275 samples. In 224 distinct orderings of mutated genes, mutations related to DNA methylation typically preceded those related to cell signaling, but signaling-first cases did occur, and had higher peripheral cell counts, increased signaling mutation homozygosity, and younger patient age. Serial sample analysis suggested that NPM1 and DNA methylation mutations provide an advantage to signaling mutations in AML. Interestingly, WT1 mutation evolution shared features with signaling mutations, such as WT1-early being proliferative and occurring in younger individuals, trends that remained in multivariable regression. Some mutation orderings had a worse prognosis, but this was mediated by unfavorable mutations, not mutation order. These findings add a dimension to the mutation landscape of AML, identifying uncommon patterns of leukemogenesis and shedding light on heterogeneous phenotypes.

Kinetochore-microtubule error correction for biorientation: lessons from yeast.

Accurate chromosome segregation in mitosis relies on sister kinetochores forming stable attachments to microtubules (MTs) extending from opposite spindle poles and establishing biorientation. To achieve this, erroneous kinetochore-MT interactions must be resolved through a process called error correction, which dissolves improper kinetochore-MT attachment and allows new interactions until biorientation is achieved. The Aurora B kinase plays key roles in driving error correction by phosphorylating Dam1 and Ndc80 complexes, while Mps1 kinase, Stu2 MT polymerase and phosphatases also regulate this process. Once biorientation is formed, tension is applied to kinetochore-MT interaction, stabilizing it. In this review article, we discuss the mechanisms of kinetochore-MT interaction, error correction and biorientation. We focus mainly on recent insights from budding yeast, where the attachment of a single MT to a single kinetochore during biorientation simplifies the analysis of error correction mechanisms.

The Changes in Relative Blood Volume During Dialysis are Characterized by Ultrafiltration Rate and Predialysis Blood Test Values.

INTRODUCTION: Continuous monitoring of relative blood volume (percentage BV) in hemodialysis (HD) is critical for determining dry weight and preventing intradialytic hypotension. However, the cause of the blood volume variation remains unknown. This research aims to examine factors that influence the percentage BV. METHODS: We devised a formula based on coefficients ("a," "τ" and "b") to predict changes in percentage BV. "a" denotes a significant decrease in percentage BV in the early stages of HD. "τ" represents the transition from early to late phase of HD. "b" denotes the slope of the decrease in percentage BV in the late phase of HD. We measured the percentage BV in 18 patients with end-stage renal disease. The coefficients were estimated by fitting experimental data from patients using a least squares optimization algorithm. A correlation analysis of these parameters and patient predialysis data was performed. RESULTS: Ultrafiltration rate (UFR) was found to be negatively correlated with "b" (r = -0.851, p < 0.01). However, UFR was not significantly related to "a." Predialysis serum total protein level was negatively correlated with "a" (r = -0.531, p = 0.042). Predialysis serum albumin and predialysis sodium were not significantly correlated with "a" and "τ". Plasma osmolarity did not have a significant relationship with "a" and "τ". DISCUSSION/CONCLUSION: UFR influenced the decrease in percentage BV in the late phase but did not influence the decrease of percentage BV in the early phase. "a" was associated with predialysis serum total protein level level but not with plasma osmolality or predialysis sodium. This implies that colloid oncotic pressure is important for plasma refilling immediately after dialysis begins.During the change of percentage BV, the decrease in the early phase of dialysis was not related to UFR, but related to other parameters, especially predialysis total protein level. A decrease in the late phase of dialysis is related to UFR.

Predictive Insights Into Exocrine Pancreatic Insufficiency in Chronic Pancreatitis and Autoimmune Pancreatitis: A Decision Tree Approach.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is a common manifestation of chronic pancreatitis (CP) and autoimmune pancreatitis (AIP). This study aimed to estimate the presence of EPI in patients with CP or AIP using alternative clinical markers. MATERIALS AND METHODS: A machine learning analysis employing a decision tree model was conducted on a retrospective training cohort comprising 57 patients with CP or AIP to identify EPI, defined as fecal elastase-1 levels less than 200 µg/g. The outcomes were then confirmed in a validation cohort of 26 patients. RESULTS: Thirty-nine patients (68%) exhibited EPI in the training cohort. The decision tree algorithm revealed body mass index (≤21.378 kg/m 2 ) and total protein level (≤7.15 g/dL) as key variables for identifying EPI. The algorithm's performance was assessed using 5-fold cross-validation, yielding area under the receiver operating characteristic curve values of 0.890, 0.875, 0.750, 0.625, and 0.771, respectively. The results from the validation cohort closely replicated those in the training cohort. CONCLUSIONS: Decision tree analysis revealed that EPI in patients with CP or AIP can be identified based on body mass index and total protein. These findings may help guide the implementation of appropriate treatments for EPI.

Time-resolved serial crystallography to track the dynamics of carbon monoxide in the active site of cytochrome c oxidase.

Cytochrome c oxidase (CcO) is part of the respiratory chain and contributes to the electrochemical membrane gradient in mitochondria as well as in many bacteria, as it uses the energy released in the reduction of oxygen to pump protons across an energy-transducing biological membrane. Here, we use time-resolved serial femtosecond crystallography to study the structural response of the active site upon flash photolysis of carbon monoxide (CO) from the reduced heme a3 of ba3-type CcO. In contrast with the aa3-type enzyme, our data show how CO is stabilized on CuB through interactions with a transiently ordered water molecule. These results offer a structural explanation for the extended lifetime of the CuB-CO complex in ba3-type CcO and, by extension, the extremely high oxygen affinity of the enzyme.

Mutation order in acute myeloid leukemia identifies uncommon patterns of evolution and illuminates phenotypic heterogeneity.

Acute myeloid leukemia (AML) has a poor prognosis and a heterogeneous mutation landscape. Although common mutations are well-studied, little research has characterized how the sequence of mutations relates to clinical features. Using published, single-cell DNA sequencing data from three institutions, we compared clonal evolution patterns in AML to patient characteristics, disease phenotype, and outcomes. Mutation trees, which represent the order of select mutations, were created for 207 patients from targeted panel sequencing data using 1 639 162 cells, 823 mutations, and 275 samples. In 224 distinct orderings of mutated genes, mutations related to DNA methylation typically preceded those related to cell signaling, but signaling-first cases did occur, and had higher peripheral cell counts, increased signaling mutation homozygosity, and younger patient age. Serial sample analysis suggested that NPM1 and DNA methylation mutations provide an advantage to signaling mutations in AML. Interestingly, WT1 mutation evolution shared features with signaling mutations, such as WT1-early being proliferative and occurring in younger individuals, trends that remained in multivariable regression. Some mutation orderings had a worse prognosis, but this was mediated by unfavorable mutations, not mutation order. These findings add a dimension to the mutation landscape of AML, identifying uncommon patterns of leukemogenesis and shedding light on heterogenous phenotypes.

Visualizing the DNA repair process by a photolyase at atomic resolution.

Photolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci. We used these results to create a movie that depicts the repair of CPD lesions in the picosecond-to-nanosecond range, followed by the recovery of the enzymatic moieties involved in catalysis, completing the formation of the fully reduced enzyme-product complex at 500 nanoseconds. Finally, back-flip intermediates of the thymine bases to reanneal the DNA were captured at 25 to 200 microseconds. Our data cover the complete molecular mechanism of a photolyase and, importantly, its chemistry and enzymatic catalysis at work across a wide timescale and at atomic resolution.

Chromosome biorientation requires Aurora B's spatial separation from its outer kinetochore substrates, but not its turnover at kinetochores.

For correct chromosome segregation in mitosis, sister kinetochores must interact with microtubules from opposite spindle poles (biorientation). For this, aberrant kinetochore-microtubule interaction must be resolved (error correction) by Aurora B kinase. Once biorientation is formed, tension is applied on kinetochore-microtubule interaction, stabilizing this interaction. The mechanism for this tension-dependent process has been debated. Here, we study how Aurora B localizations at different kinetochore sites affect the biorientation establishment and maintenance in budding yeast. Without the physiological Aurora B-INCENP recruitment mechanisms, engineered recruitment of Aurora B-INCENP to the inner kinetochore, but not to the outer kinetochore, prior to biorientation supports the subsequent biorientation establishment. Moreover, when the physiological Aurora B-INCENP recruitment mechanisms are present, an engineered Aurora B-INCENP recruitment to the outer kinetochore, but not to the inner kinetochore, during metaphase (after biorientation establishment) disrupts biorientation, which is dependent on the Aurora B kinase activity. These results suggest that the spatial separation of Aurora B from its outer kinetochore substrates is required to stabilize kinetochore-microtubule interaction when biorientation is formed and tension is applied on this interaction. Meanwhile, Aurora B exhibits dynamic turnover on the centromere/kinetochore during early mitosis, a process thought to be crucial for error correction and biorientation. However, using the engineered Aurora B-INCENP recruitment to the inner kinetochore, we demonstrate that, even without such a turnover, Aurora B-INCENP can efficiently support biorientation. Our study provides important insights into how Aurora B promotes error correction for biorientation in a tension-dependent manner.

Proteome insights of citric acid-mediated cadmium toxicity tolerance in Brassica napus L.

Cadmium (Cd) is a toxic substance that is uptake by plants from soils, Cd easily transfers into the food chain. Considering global food security, eco-friendly, cost-effective, and metal detoxification strategies are highly demandable for sustainable food crop production. The purpose of this study was to investigate how citric acid (CA) alleviates or tolerates Cd toxicity in Brassica using a proteome approach. In this study, the global proteome level was significantly altered under Cd toxicity with or without CA supplementation in Brassica. A total of 4947 proteins were identified using the gel-free proteome approach. Out of these, 476 proteins showed differential abundance between the treatment groups, wherein 316 were upregulated and 160 were downregulated. The gene ontology analysis reveals that differentially abundant proteins were involved in different biological processes including energy and carbohydrate metabolism, CO2 assimilation and photosynthesis, signal transduction and protein metabolism, antioxidant defense, heavy metal detoxification, plant development, and cytoskeleton and cell wall structure in Brassica leaves. Interestingly, several candidate proteins such as superoxide dismutase (A0A078GZ68) L-ascorbate peroxidase 3 (A0A078HSG4), glutamine synthetase (A0A078HLB2), glutathione S-transferase DHAR1 (A0A078HPN8), glutamine synthetase (A0A078HLB2), cysteine synthase (A0A078GAD3), S-adenosylmethionine synthase 2 (A0A078JDL6), and thiosulfate/3-mercaptopyruvate sulfur transferase 2 (A0A078H905) were involved in antioxidant defense system and sulfur assimilation-involving Cd-detoxification process in Brassica. These findings provide new proteome insights into CA-mediated Cd-toxicity alleviation in Brassica, which might be useful to oilseed crop breeders for enhancing heavy metal tolerance in Brassica using the breeding program, with sustainable and smart Brassica production in a metal-toxic environment.

A versatile approach to high-density microcrystals in lipidic cubic phase for room-temperature serial crystallography.

Serial crystallography has emerged as an important tool for structural studies of integral membrane proteins. The ability to collect data from micrometre-sized weakly diffracting crystals at room temperature with minimal radiation damage has opened many new opportunities in time-resolved studies and drug discovery. However, the production of integral membrane protein microcrystals in lipidic cubic phase at the desired crystal density and quantity is challenging. This paper introduces VIALS (versatile approach to high-density microcrystals in lipidic cubic phase for serial crystallography), a simple, fast and efficient method for preparing hundreds of microlitres of high-density microcrystals suitable for serial X-ray diffraction experiments at both synchrotron and free-electron laser sources. The method is also of great benefit for rational structure-based drug design as it facilitates in situ crystal soaking and rapid determination of many co-crystal structures. Using the VIALS approach, room-temperature structures are reported of (i) the archaerhodopsin-3 protein in its dark-adapted state and 110 ns photocycle intermediate, determined to 2.2 and 1.7 Å, respectively, and (ii) the human A2A adenosine receptor in complex with two different ligands determined to a resolution of 3.5 Å.

Mapping protein dynamics at high spatial resolution with temperature-jump X-ray crystallography.

Understanding and controlling protein motion at atomic resolution is a hallmark challenge for structural biologists and protein engineers because conformational dynamics are essential for complex functions such as enzyme catalysis and allosteric regulation. Time-resolved crystallography offers a window into protein motions, yet without a universal perturbation to initiate conformational changes the method has been limited in scope. Here we couple a solvent-based temperature jump with time-resolved crystallography to visualize structural motions in lysozyme, a dynamic enzyme. We observed widespread atomic vibrations on the nanosecond timescale, which evolve on the submillisecond timescale into localized structural fluctuations that are coupled to the active site. An orthogonal perturbation to the enzyme, inhibitor binding, altered these dynamics by blocking key motions that allow energy to dissipate from vibrations into functional movements linked to the catalytic cycle. Because temperature jump is a universal method for perturbing molecular motion, the method demonstrated here is broadly applicable for studying protein dynamics.

Genome sequencing reveals the genetic architecture of heterostyly and domestication history of common buckwheat.

Common buckwheat, Fagopyrum esculentum, is an orphan crop domesticated in southwest China that exhibits heterostylous self-incompatibility. Here we present chromosome-scale assemblies of a self-compatible F. esculentum accession and a self-compatible wild relative, Fagopyrum homotropicum, together with the resequencing of 104 wild and cultivated F. esculentum accessions. Using these genomic data, we report the roles of transposable elements and whole-genome duplications in the evolution of Fagopyrum. In addition, we show that (1) the breakdown of heterostyly occurs through the disruption of a hemizygous gene jointly regulating the style length and female compatibility and (2) southeast Tibet was involved in common buckwheat domestication. Moreover, we obtained mutants conferring the waxy phenotype for the first time in buckwheat. These findings demonstrate the utility of our F. esculentum assembly as a reference genome and promise to accelerate buckwheat research and breeding.

Regulation of Osteoblast to Osteocyte Differentiation by Cyclin-Dependent Kinase-1.

Osteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The purpose of this study is to identify cell cycle regulators involved in the differentiation of osteoblasts into osteocytes and determine their physiological significance. The study uses IDG-SW3 cells as a model for the differentiation from osteoblasts to osteocytes. Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. Inhibition of CDK1 activity reduces IDG-SW3 cell proliferation and differentiation into osteocytes. Osteocyte and Osteoblast-specific Cdk1 knockout in mice (Dmp1-Cdk1KO ) results in trabecular bone loss. Pthlh expression increases during differentiation, but inhibiting CDK1 activity reduces Pthlh expression. Parathyroid hormone-related protein concentration is reduced in the bone marrow of Dmp1-Cdk1KO mice. Four weeks of Parathyroid hormone administration partially recovers the trabecular bone loss in Dmp1-Cdk1KO mice. These results demonstrate that Cdk1 plays an essential role in the differentiation from osteoblast to osteocyte and the acquisition and maintenance of bone mass. The findings contribute to a better understanding of the mechanisms of bone mass regulation and can help develop efficient therapeutic strategies for osteoporosis treatment.

Clonal evolution and hierarchy in myeloid malignancies.

Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the intricacies of clonal evolution in myeloid malignancies and its implications for the development of new diagnostic and therapeutic approaches.

A Phase Ib/II Study of Ivosidenib with Venetoclax ± Azacitidine in IDH1-Mutated Myeloid Malignancies.

The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached. Composite complete remission with IVO + VEN + AZA versus IVO + VEN was 90% versus 83%. Among measurable residual disease (MRD)-evaluable patients (N = 16), 63% attained MRD--negative remissions; IDH1 mutation clearance occurred in 64% of patients receiving ≥5 treatment cycles (N = 14). Median event-free survival and overall survival were 36 [94% CI, 23-not reached (NR)] and 42 (95% CI, 42-NR) months. Patients with signaling gene mutations appeared to particularly benefit from the triplet regimen. Longitudinal single-cell proteogenomic analyses linked cooccurring mutations, antiapoptotic protein expression, and cell maturation to therapeutic sensitivity of IDH1-mutated clones. No IDH isoform switching or second-site IDH1 mutations were observed, indicating combination therapy may overcome established resistance pathways to single-agent IVO. SIGNIFICANCE: IVO + VEN + AZA is safe and active in patients with IDH1-mutated myeloid malignancies. Combination therapy appears to overcome resistance mechanisms observed with single-agent IDH-inhibitor use, with high MRD-negative remission rates. Single-cell DNA ± protein and time-of-flight mass-cytometry analysis revealed complex resistance mechanisms at relapse, highlighting key pathways for future therapeutic intervention. This article is highlighted in the In This Issue feature, p. 247.

Targeting MCL1-driven anti-apoptotic pathways to overcome hypomethylating agent resistance in RAS -mutated chronic myelomonocytic leukemia.

RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Using single-cell, multi-omics technologies, we sought to dissect the biological mechanisms underlying the initiation and progression of RAS pathway-mutated CMML. We found that RAS pathway mutations induced the transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs), which underwent proliferation and monocytic differentiation in response to cell-intrinsic and -extrinsic inflammatory signaling that also impaired immune cells' functions. HSPCs expanded at disease progression and relied on the NF- K B pathway effector MCL1 to maintain their survival, which explains why patients with RAS pathway- mutated CMML do not benefit from BCL2 inhibitors such as venetoclax. Our study has implications for developing therapies to improve the survival of patients with RAS pathway- mutated CMML.

Phase 1 study of oral selective estrogen receptor degrader (SERD) amcenestrant (SAR439859), in Japanese women with ER-positive and HER2-negative advanced breast cancer (AMEERA-2).

BACKGROUND: This AMEERA-2 study evaluated the pharmacokinetics, efficacy, and safety of the oral selective estrogen receptor degrader amcenestrant as a monotherapy with dose escalation in Japanese postmenopausal women with advanced estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer. METHODS: In this open-label, nonrandomized, phase I study, patients received amcenestrant 400 mg once daily (QD) (n = 7) and 300 mg twice daily (BID) (n = 3). The incidence of dose-limiting toxicities (DLT), recommended dose, maximum tolerated dose (MTD), pharmacokinetics, efficacy, and safety were assessed. RESULTS: No DLTs were observed and MTD was not reached in the 400 mg QD group. One DLT (grade 3 maculopapular rash) was reported in a patient treated with 300 mg BID. After repeated oral administration of either dosing regimen, steady state reached before day 8, without accumulation. Four out of 5 response-evaluable patients from 400 mg QD group achieved clinical benefit and showed tumor shrinkage. No clinical benefit was reported in the 300 mg BID group. Overall, most patients (8/10) experienced a treatment-related adverse event (TRAE), with skin and subcutaneous tissue disorders most commonly reported (4/10 patients). No ≥ grade 3 TRAE in 400 mg QD group and 1 grade 3 TRAE in 300 mg BID group were reported. CONCLUSIONS: Amcenestrant 400 mg QD has a favorable safety profile and has been selected as the recommended Phase II dose for monotherapy for evaluating the safety and efficacy of amcenestrant in a larger, global, randomized clinical trial of patients with metastatic breast cancer. TRIAL REGISTRATION: Clinical trial registration NCT03816839.

Insertion of ten amino acids into 13S globulin zero-repeat subunit improves trypsin digestibility in common buckwheat (Fagopyrum esculentum Moench) seeds.

The 13S globulin zero-repeat subunit is resistant to trypsin and may have higher allergenicity than the 1-6 tandem repeat subunits in common buckwheat (Fagopyrum esculentum Moench). To explore alleles useful for lowering allergenicity, amplicon deep sequencing targeting the zero-repeat subunit gene was conducted in bulked genomic DNA from eight cultivars and landraces. The analysis identified a unique allele encoding a zero-repeat subunit with 10 amino acid insertion (10aa) at a position equivalent to the tandem repeat insertion. Prediction of its 3-D structure suggested that 10aa changes the ß-hairpin structure in the non-10aa (native) subunit to a random coil, which is also found in 1- and 3- repeat subunits. Homozygotes of the 10aa allele were developed and showed that the 10aa subunit was more digestible than the native subunit. However, the 10aa subunit was still less digestible than the 1-6 repeat subunits, suggesting needs to explore unfunctional alleles.

Risk factors for recurrence and regrowth of spinal schwannoma.

BACKGROUND: Spinal schwannoma recurs after initial surgery at a rate of 4%-6%, with known risk factors including subtotal resection, multilevel involvement, large tumor size, and malignant histopathology. This study examined risk factors for schwannoma recurrence and residual tumor regrowth. METHODS: Sixty-five patients who underwent resection of spinal schwannoma in our department between July 2010 and December 2018 and were followed up for more than 1 year were retrospectively analyzed for age, sex, follow-up duration, imaging and surgical data, recurrence, reoperation, and Japanese Orthopaedic Association scores before and 1 year after surgery. Patients with postoperative recurrence or residual tumor regrowth of >10% at the final visit (R+ group) were compared with patients without recurrence or regrowth (R- group). Multivariate logistic regression analysis was performed to analyze concurrent effects of risk factors on recurrence and regrowth. RESULTS: The 65 patients (mean age 52.4 years at surgery) had schwannomas involving cervical (n = 14), thoracic (n = 25), and lumbar (n = 26) spinal levels. Mean follow-up duration was 58 months. Location was intradural in 65%, extradural in 17%, and both intradural and extradural in 18%. There were 4 recurrences (6.2%), and the mean interval between surgery and recurrence was 18.8 months. Seven patients (10.8%) experienced regrowth. Comparing group R+ (n = 11) and group R- (n = 54), univariate analysis showed significant differences in Sridhar tumor classification, giant tumor (Sridhar classification II, IVb, and V), left-right and cranial-caudal tumor size, largest diameter, operative time, blood loss, subtotal resection, reoperation, fusion surgery, and follow-up duration. Multivariate logistic regression analysis revealed giant tumor (Sridhar classification types II, IVb, and V) as an independent risk factor for recurrence and regrowth. CONCLUSIONS: This retrospective review of 65 consecutive patients with spinal schwannoma in a single institution demonstrated that 16.9% had recurrence or regrowth, demonstrating that this potential risk should be kept in mind.