Donor matters: Donor selection impact on hematopoietic stem cell transplantation outcomes in Hispanic patients with B-cell acute lymphocytic leukemia: Insights from a myeloablative HSCT study.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. RESULTS: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). CONCLUSION: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.

How I diagnose and manage VEXAS syndrome.

OBJECTIVES: To discuss VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, including the clinical and pathologic features, diagnostic challenges, and treatment options. METHODS: A case-based approach and pertinent literature review were used to highlight the features of VEXAS syndrome, describe how to make the diagnosis, and discuss available therapies. RESULTS: VEXAS syndrome is an adult-onset, progressive systemic inflammatory disorder with overlapping rheumatologic and hematologic manifestations, including an increased risk of myelodysplastic neoplasms and plasma cell neoplasms. The disorder is associated with a somatic mutation of the X-linked UBA1 gene involved in ubiquitylation, typically involving p.Met41; however, rare variations have been identified outside this region. Patients often present with complex histories and see physicians from multiple specialties before receiving the diagnosis, which is often delayed. Symptoms are related to inflammation as well as cytopenias, particularly macrocytic anemia. Characteristic cytoplasmic vacuoles are present in myeloid (granulocytic, monocytic) and erythroid precursors in the vast majority of cases. CONCLUSIONS: Either clinicians or pathologists may suspect a diagnosis of VEXAS syndrome depending on the clinical presentation and bone marrow findings. More studies are needed to determine the best therapeutic options, which are currently limited.

Blast Phase of Myeloproliferative Neoplasm Resembles Acute Myeloid Leukemia, Myelodysplasia-Related, in Clinical Presentation, Cytogenetic Pattern, and Genomic Profile, and Often Undergoes Reversion to Second Chronic Phase Status After Induction Chemotherapy.

CONTEXT.­: BCR::ABL-negative myeloproliferative neoplasm (MPN) has a prolonged clinical course, and some cases eventually undergo transformation to blast phase; its pathogenesis remains to be elucidated. OBJECTIVE.­: To evaluate the clinicopathologic characteristics of MPN in blast phase. DESIGN.­: The study aimed to retrospectively analyze the clinical and laboratory data of 24 cases. RESULTS.­: Median latency to blast phase was 48 months (range, 7-384 months). Complex karyotypes were seen in 12 of the 24 cases (50%). Overall, 16 cases (66.7%) exhibited high allele burdens of MPN driver mutations along with increased blasts, consistent with linear clonal evolution, whereas the remainder (8; 33.3%) showed loss or partial loss of the driver mutation suggestive of a parallel evolution. Additional mutations were noted in 23 cases (100%), including TP53 mutations in 10 of 24 cases (41.7%). Following chemotherapy, 15 of the 24 patients (62.5%) reverted to a second chronic phase while retaining or regaining MPN driver mutations and losing blast-related mutations, although 9 of the 15 patients (60%) later died of disease progression. Median overall survival was 10 months (CI, 4.6-15.4), with those harboring complex karyotypes demonstrating decreased survival (6 versus 29 months; P = .004). CONCLUSIONS.­: MPN-blast phase resembles acute myeloid leukemia, myelodysplasia-related, in cytogenetic pattern, mutation profile, and clinical outcome. Two patterns of clonal evolution are inferred by dynamic analysis of mutation profiles: linear and parallel evolutions. Although overall survival was dismal, 62.5% of our cases achieved second chronic phase, and they showed better survival than those without second chronic phase.

Extraventricular Drain Care Bundle Decreases Cerebrospinal Fluid Infection Rates Associated With Extraventricular Drain-Related Procedures and Systemic Infection.

BACKGROUND: Infection associated with extraventricular drain (EVD)-related procedures is well known. OBJECTIVE: To investigate the impact of our institution's EVD care bundle on the infection rates associated with EVD-related procedures. METHODS: A retrospective study was conducted from June 2022 to June 2023 to compare the infection rate six months before and six months after the implantation of the EVD care bundle. RESULTS: A total of 58 patients were included in the study (n=33 patients in 2022 and n=25 patients in 2023). The infection rate was 21.2% (7/33) prior to the implementation of the EVD care bundle and 0.0% (0/25) afterward. The seven patients with cerebrospinal fluid (CSF) infection did not have a higher total number of EVD-related procedures compared to the other 26 patients without CSF infection (8.0 vs. 9.4, p=0.7364); however, the mean number of EVD replacements was higher in patients with CSF infection (1.4 vs. 3.4, p=0.0028). The total number of EVD-related procedures was not different between 2022 and 2023 (8.3 vs. 5.2, respectively, p=0.1892); however, the mean number of EVD replacements was lower in 2023 (1.8 vs. 1.0, p=0.0257). In 2022, 22/33 patients had systemic infection, among which 7/22 also had CSF infection. In 2023, 13/25 patients had a systemic infection, among which 0/13 had CSF infection. CONCLUSIONS: The EVD care bundle consisting of standardizations, checklists, and monitoring reduces the CSF infection rates associated with EVD-related procedures and systemic infection.

A translation proofreader of archaeal origin imparts multi-aldehyde stress tolerance to land plants.

Aldehydes, being an integral part of carbon metabolism, energy generation, and signalling pathways, are ingrained in plant physiology. Land plants have developed intricate metabolic pathways which involve production of reactive aldehydes and its detoxification to survive harsh terrestrial environments. Here, we show that physiologically produced aldehydes, i.e., formaldehyde and methylglyoxal in addition to acetaldehyde, generate adducts with aminoacyl-tRNAs, a substrate for protein synthesis. Plants are unique in possessing two distinct chiral proofreading systems, D-aminoacyl-tRNA deacylase1 (DTD1) and DTD2, of bacterial and archaeal origins, respectively. Extensive biochemical analysis revealed that only archaeal DTD2 can remove the stable D-aminoacyl adducts on tRNA thereby shielding archaea and plants from these system-generated aldehydes. Using Arabidopsis as a model system, we have shown that the loss of DTD2 gene renders plants susceptible to these toxic aldehydes as they generate stable alkyl modification on D-aminoacyl-tRNAs, which are recycled only by DTD2. Bioinformatic analysis identifies the expansion of aldehyde metabolising repertoire in land plant ancestors which strongly correlates with the recruitment of archaeal DTD2. Finally, we demonstrate that the overexpression of DTD2 offers better protection against aldehydes than in wild type Arabidopsis highlighting its role as a multi-aldehyde detoxifier that can be explored as a transgenic crop development strategy.

Concordance of Next-Generation Sequencing and Multiparametric Flow Cytometry Methods for Detecting Measurable Residual Disease in Adult Acute Lymphoblastic Leukemia: Optimizing Prediction of Clinical Outcomes From a Single-Center Study.

INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.

Radiomics Correlation to CD68+ Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is the ninth most common cancer worldwide, with clear cell RCC (ccRCC) being the most frequent histological subtype. The tumor immune microenvironment (TIME) of ccRCC is an important factor to guide treatment, but current assessments are tissue-based, which can be time-consuming and resource-intensive. In this study, we used radiomics extracted from clinically performed computed tomography (CT) as a noninvasive surrogate for CD68 tumor-associated macrophages (TAMs), a significant component of ccRCC TIME. METHODS: TAM population was measured by CD68+/PanCK+ ratio and tumor-TAM clustering was measured by normalized K function calculated from multiplex immunofluorescence (mIF). A total of 1,076 regions on mIF slides from 78 patients were included. Radiomic features were extracted from multiphase CT of the ccRCC tumor. Statistical machine learning models, including random forest, Adaptive Boosting, and ElasticNet, were used to predict TAM population and tumor-TAM clustering. RESULTS: The best models achieved an area under the ROC curve of 0.81 (95% CI: [0.69, 0.92]) for TAM population and 0.77 (95% CI: [0.66, 0.88]) for tumor-TAM clustering, respectively. CONCLUSION: Our study demonstrates the potential of using CT radiomics-derived imaging markers as a surrogate for assessment of TAM in ccRCC for real-time treatment response monitoring and patient selection for targeted therapies and immunotherapies.

Spontaneous Intracerebral Hemorrhage Secondary to a Parasagittal Meningioma: A Case Report and Review of the Literature.

Meningiomas are the most prevalent tumors within the central nervous system, with most exhibiting benign characteristics. While they are often discovered incidentally, their growth can lead to symptoms such as headaches, visual changes, dizziness, and seizures. Intratumoral hemorrhage (ITH) within meningiomas is a rare occurrence. This phenomenon carries a poor prognosis, as evidenced by significant rates of morbidity and mortality. This case report describes a unique case of a 52-year-old male who experienced a spontaneous right parietal lobe intracerebral hemorrhage adjacent to the superior sagittal sinus. Subsequent investigations revealed this to be an ITH due to an underlying WHO-grade I meningioma. This case emphasizes that while ITH in meningiomas is rare, prompt recognition and surgical intervention ensure optimal patient outcomes.

The Use of Induction Sensors and Helmet-Based Shielding Technology to Identify Differences in Electromagnetic Fields in Patients With Cranial Neurological Disease Versus Healthy Controls.

Background and objective Electromagnetic fields (EMFs) stemming from neural circuits have been evaluated in healthy human subjects by using non-invasive induction sensor technologies with adjunctive shielding constrained to a helmet constructed of Mu-metal and copper mesh. These EMF measurements have been analyzed and discerned to alter physiological states of movement, thoughts of movement, emotional thoughts, and planned activities. However, these technologies have not yet been investigated as a diagnostic tool in patients with cranial neurological pathology to evaluate differences in patterns in the pathologic state compared to healthy controls. In light of this, we conducted this study to address this scarcity of data. Methods An observational study was conducted in which patients at a single center with cranial neurological disease of all causes were eligible to enroll; they had real-time non-invasive continuous EMF measurements obtained using induction sensors and a shielded helmet. These measurements were obtained in the resting state and then compared to previously obtained measurements in healthy volunteers. Post-processing analysis was conducted to evaluate the derivatives of these EMFs to identify changes in patterns. Results Fourteen patients with traumatic injury, stroke, and neoplasm with ages ranging from 14 to 81 years underwent successful analysis and post-processing of their cortically generated EMF waves. Patterns of EMF waves were compared to previously obtained data from four healthy controls. It was identified that there was less variation in the EMF measurements in patients with neurological disease compared to healthy controls. This was identified based on differences in derivatives of the EMF waves and decreased numbers of peaks and valleys in the EMF waves. Conclusions Novel induction sensors with an engineered, layered Mu-metal and copper mesh helmet for shielding with Mu-metal EMF channels appear to be efficient in measuring neural circuit-driven EMF non-invasively, in real-time, and continuously and can discern differences in EMF patterns between healthy volunteers and patients with neural circuit pathology. The decreased variability in EMF measurements in patients with neural pathology and greater decreases in slope within low-frequency measurements may be correlated with disrupted neural signaling from dysfunctional neurons and abnormalities in spatial and temporal summation. Some EMF changes in ill individuals correspond to changes in the experimentally induced lesions in the animal model. Further studies are warranted to devise models of disease and healthy states to improve these technologies as a diagnostic modality.

A Right-Sided Approach to Anterior Communicating Artery Aneurysms: A Case Review and Technical Report.

Anterior communicating artery (ACoA) aneurysms are the most frequently encountered type of intracranial aneurysm. ACoA aneurysms may require treatment depending on clinical presentation, size, risk of rupture, and ruptured status. In patients where treatment is indicated, options entail endovascular securement or clipping. Under the clipping umbrella, surgical approaches traditionally entail a pterional craniotomy and its modifications such as the lateral supraorbital approach. Sidedness of this craniotomy has been a topic of debate. To discuss this we present a case and technical report with nuances of the approach wherein a 48-year-old female presented with the worst headache of her life. The patient was found to have a ruptured wide-necked 7.2 x 8.1 x 5.8 mm ACoA aneurysm more eccentric to the left and fed from the left A1 intertwined with a frontopolar branch, numerous perforators and the recurrent artery of Heubner. The patient underwent a successful clipping from a right-sided approach. As such, with appropriate skull base drilling, exposure, optimization of brain relaxation, and a generous opening of the Sylvian fissure bilateral internal carotid arteries, anterior cerebral arteries with both A1 and A2 segments, middle cerebral arteries, the ACoA, and the relevant anatomy can be appropriately visualized from a right-sided approach. Therefore, an approach is described to optimize exposure to allow for nearly all anterior communicating aneurysms to be clipped from a right-sided pterional approach.

Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

PURPOSE: Our preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen. PATIENTS AND METHODS: Patients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on Days 1, 2, 8, 9, 15, and 16. Patients received 40 mg Dex and 1.5 mg/m2 BZ on Days 1, 8, and 15. Cycles were repeated every 28 days. Pre- and posttreatment bone marrow specimens (IHC, n = 9; imaging mass cytometry, n = 6) and peripheral blood samples were collected for analysis (flow cytometry, n = 5; T-cell receptor clonality, n = 7; cytokine assay, n = 7). RESULTS: PELA/BZ/Dex was well-tolerated in all patients. Treatment-emergent toxicities were transient, and no dose-limiting toxicities occurred. Six (55%) of 11 response-evaluable patients showed decreased paraprotein. Treatment increased T and natural killer cell activation, inflammatory cytokine release, and programmed death-ligand 1 expression in bone marrow. Compared with nonresponders, responders had higher reovirus protein levels, increased cytotoxic T-cell infiltration posttreatment, cytotoxic T cells in significantly closer proximity to multiple myeloma cells, and larger populations of a novel immune-primed multiple myeloma phenotype (CD138+ IDO1+HLA-ABCHigh), indicating immunomodulation. CONCLUSIONS: PELA/BZ/Dex is well-tolerated and associated with anti-multiple myeloma activity in a subset of responding patients, characterized by immune reprogramming and TiME changes, warranting further investigation of PELA as an immunomodulator.

Distinct localization of chiral proofreaders resolves organellar translation conflict in plants.

Plants have two endosymbiotic organelles originated from two bacterial ancestors. The transition from an independent bacterium to a successful organelle would have required extensive rewiring of biochemical networks for its integration with archaeal host. Here, using Arabidopsis as a model system, we show that plant D-aminoacyl-tRNA deacylase 1 (DTD1), of bacterial origin, is detrimental to organellar protein synthesis owing to its changed tRNA recognition code. Plants survive this conflict by spatially restricting the conflicted DTD1 to the cytosol. In addition, plants have targeted archaeal DTD2 to both the organelles as it is compatible with their translation machinery due to its strict D-chiral specificity and lack of tRNA determinants. Intriguingly, plants have confined bacterial-derived DTD1 to work in archaeal-derived cytosolic compartment whereas archaeal DTD2 is targeted to bacterial-derived organelles. Overall, the study provides a remarkable example of the criticality of optimization of biochemical networks for survival and evolution of plant mitochondria and chloroplast.

Cellular Mechanisms of Electromagnetic Field in Traumatic Brain Injury.

This paper presents a comprehensive review of the extant literature from 1980 through 2023 on the role and utility of Electromagnetic Fields (EMF) in the treatment of brain trauma and brain neuropathology resulting from disease. Brain trauma resulting from accident, injury and disease is a significant contributor to short and long-term morbidity, as well as a leading cause of mortality globally. To date, limited effective treatments strategies exist, and are focused primarily on symptom relief, not restoring primary preinjury function and structure. Much of the current clinical literature is based on retrospective case reports and limited animal model prospective trials exploring core etiology and alterations in post-injury clinical phenotypes. The current findings reported in the scientific literature suggest that electromagnetic therapy may hold promise as a potential non-invasive treatment for traumatic brain injury and neuropathology. Although promising, well designed clinical trials are needed to better determine its potential clinical effectiveness in this diverse patient population. Future trials will need to determine the impact of clinical variables, such as sex, age, type and extent of injury and pathology, pre-injury baseline health status and a comprehensive biopsychosocial assessment to determine a more effective personalized approach to patient care. Although initially showing promise, much work needs to be done.

Neurosurgical Outcomes in Severe Traumatic Brain Injuries Between Service Lines: Review of a Single Institution Database.

Severe traumatic injury (sTBI) continues to be a common source of morbidity and mortality. While there have been several advances in understanding the pathophysiology of this injury, the clinical outcome has remained grim. These trauma patients often require multidisciplinary care and are admitted to a surgical service line, depending on hospital policy. A retrospective chart review spanning 2019-2022 was completed using the electronic health record of the neurosurgery service. We identified 140 patients with a Glasgow Coma Scale (GCS) of eight or less, ages 18-99, who were admitted to a level-one trauma center in Southern California. Seventy patients were admitted under the neurosurgery service, while the other half were admitted to the surgical intensive care unit (SICU) service after initial assessment in the emergency department by both services to evaluate for multisystem injury. Between both groups, the injury severity scores that evaluated patients' overall injuries were not significantly different. The results demonstrate a significant difference in GCS change, modified Rankin Scale (mRS) change, and Glasgow Outcome Scale (GOS) change between the two groups. Furthermore, the mortality rate differed between neurosurgical care and other service care by 27% and 51%, respectively, despite similar Injury Severity Scores (ISS) (p=0.0026). Therefore, this data demonstrates that a well-trained neurosurgeon with critical care experience can safely manage a severe traumatic brain injury patient with an isolated head injury as a primary service while in the intensive care unit. Since injury severity scores did not differ between these two service lines, we further theorize that this is likely due to a deep understanding of the nuances of neurosurgical pathophysiology and Brain Trauma Foundation (BTF) guidelines.

Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study.

INTRODUCTION: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers. METHODS: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance. RESULTS: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86). CONCLUSIONS: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication.

Chronic Lymphocytic Leukemia With Two B-Cell Populations of Discordant Light Chain Restrictions in Individual Patients: Parallel Development of Biclonal B-Cell Neoplasms or Clonal Evolution With Isotype Switch?

OBJECTIVES: To evaluate clinicopathologic characteristics of biclonal chronic lymphocytic leukemia (CLL). METHODS: Retrospectively analyze clinical data and pathologic features. RESULTS: Ten cases were identified in which flow cytometry demonstrated an abnormal B-cell population with a CLL-like immunophenotype but showed no definitive light chain restriction. All had cytogenetic abnormalities detected, including seven with two CLL-related abnormalities. Four of these showed features suggestive of clonal evolution, all having del(13q) as a "stem-line" abnormality and three showing del(11q) as a "side-line" abnormality. Five (50%) cases demonstrated deleterious NOTCH1 mutations, in contrast to 11.8% in a control group of monoclonal CLL (P < .05). Of the 10 patients, 5 received treatment, with good/partial response in three cases and therapeutic resistance in one case. The median treatment-free survival was estimated at 68 months. CONCLUSIONS: Despite a polytypic pattern of light chain expression, the neoplastic nature of biclonal CLL is suggested by a characteristic CLL phenotype and can be confirmed by cytogenetic and genomic analyses. The two clones with discordant light chain isotypes may share a "stem-line" cytogenetic abnormality, suggesting possible clonal evolution. Biclonal CLL is associated with NOTCH1 mutations, which may occur in a small subclone and gradually evolve in clonal size. Genomic analysis on light chain-sorted and/or chronologically collected samples may provide insight into clonal evolution in CLL.

The FANCC-FANCE-FANCF complex is evolutionarily conserved and regulates meiotic recombination.

At meiosis, programmed meiotic DNA double-strand breaks are repaired via homologous recombination, resulting in crossovers (COs). From a large excess of DNA double-strand breaks that are formed, only a small proportion gets converted into COs because of active mechanisms that restrict CO formation. The Fanconi anemia (FA) complex proteins AtFANCM, MHF1 and MHF2 were previously identified in a genetic screen as anti-CO factors that function during meiosis in Arabidopsis thaliana. Here, pursuing the same screen, we identify FANCC as a new anti-CO gene. FANCC was previously only identified in mammals because of low primary sequence conservation. We show that FANCC, and its physical interaction with FANCE-FANCF, is conserved from vertebrates to plants. Further, we show that FANCC, together with its subcomplex partners FANCE and FANCF, regulates meiotic recombination. Mutations of any of these three genes partially rescues CO-defective mutants, which is particularly marked in female meiosis. Functional loss of FANCC, FANCE, or FANCF results in synthetic meiotic catastrophe with the pro-CO factor MUS81. This work reveals that FANCC is conserved outside mammals and has an anti-CO role during meiosis together with FANCE and FANCF.

The Fanconi Anemia (FA) pathway is the subject of intense interest owing to the role of FA as a tumor suppressor. Three FA complex proteins, FANCM, MHF1 and MHF2, were identified as factors that suppress crossover during meiosis in the model plant Arabidopsis thaliana. Here, the authors extended these findings and identified a novel anti-crossover factor and showed that it encodes the plant FANCC homolog, which was previously thought to be vertebrate-specific. They further showed that FANCC regulates meiotic crossover together with two other FA proteins, FANCE and FANCF. This suggests that the FANCC­E­F subcomplex was already regulating DNA repair in the common ancestor of all living eukaryotes.