Sequence and epigenetic variations of R2R3-MYB transcription factors determine the diversity of taproot skin and flesh colors in different cultivated types of radish (Raphanus sativus L.).

KEY MESSAGE: This study found that three paralogous R2R3-MYB transcription factors exhibit functional divergence among different subspecies and cultivated types in radish. Cultivated radish taproots exhibit a wide range of color variations due to unique anthocyanin accumulation patterns in various tissues. This study investigated the universal principles of taproot color regulation that developed during domestication of different subspecies and cultivated types. The key candidate genes RsMYB1 and RsMYB2, which control anthocyanin accumulation in radish taproots, were identified using bulked segregant analysis in two genetic populations. We introduced the RsMYB1-RsF3'H-RsMYB1Met genetic model to elucidate the complex and unstable genetic regulation of taproot flesh color in Xinlimei radish. Furthermore, we analyzed the expression patterns of three R2R3-MYB transcription factors in lines with different taproot colors and investigated the relationship between RsMYB haplotypes and anthocyanin accumulation in a natural population of 56 germplasms. The results revealed that three paralogous RsMYBs underwent functional divergence during radish domestication, with RsMYB1 regulating the red flesh of Xinlimei radish, and RsMYB2 and RsMYB3 regulating the red skin of East Asian big long radish (R. sativus var. hortensis) and European small radish (R. sativus var. sativus), respectively. Moreover, RsMYB1-H1, RsMYB2-H10, and RsMYB3-H6 were identified as the primary haplotypes exerting regulatory functions on anthocyanin synthesis. These findings provide an understanding of the genetic mechanisms regulating anthocyanin synthesis in radish and offer a potential strategy for early prediction of color variations in breeding programs.

Multi-center study of COVID-19 infection in elderly patients with lymphoma: on behalf of Jiangsu Cooperative Lymphoma Group (JCLG).

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

Bacterial isolation and genome analysis of a novel Klebsiella quasipneumoniae phage in southwest China's karst area.

BACKGROUND: Southwest China is one of the largest karst regions in the world. Karst environment is relatively fragile and vulnerable to human activities. Due to the discharge of sewage and domestic garbage, the karst system may be polluted by pathogenic bacteria. The detection of bacterial distribution and identification of phage capable of infecting them is an important approach for environmental assessment and resource acquisition. METHODS: Bacteria and phages were isolated from karst water in southwest China using the plate scribing and double plate method, respectively. Isolated phage was defined by transmission electron microscopy, one-step growth curve and optimal multiplicity of infection (MOI). Genomic sequencing, phylogenetic analysis, comparative genomic and proteomic analysis were performed. RESULTS: A Klebsiella quasipneumoniae phage was isolated from 32 isolates and named KL01. KL01 is morphologically identified as Caudoviricetes with an optimal MOI of 0.1, an incubation period of 10 min, and a lysis period of 60 min. The genome length of KL01 is about 45 kb, the GC content is 42.5%, and it contains 59 open reading frames. The highest average nucleotide similarity between KL01 and a known Klebsiella phage 6939 was 83.04%. CONCLUSIONS: KL01 is a novel phage, belonging to the Autophagoviridae, which has strong lytic ability. This study indicates that there were not only some potential potentially pathogenic bacteria in the karst environment, but also phage resources for exploration and application.

Network pharmacology and pharmacological evaluation of Wenzheng Jiedu Powder Modified Formula for neuropathic pain relief.

This study aimed to elucidate the mechanism of Wenzheng Jiedu Powder Modified Formula (WJPMF) in treating neuropathic pain (NP). Network pharmacology and experimental verification were integrated to explore the therapeutic effects and key targets of WJPMF. Active components, corresponding target genes, and absorption, distribution, metabolism, and excretion (ADME) genes of WJPMF against NP were screened from public databases. Network analysis and molecular docking were conducted to identify key targets and verify binding abilities. In vivo experiments were performed on spared nerve injury (SNI) rats to assess the analgesic effects and regulatory mechanisms of WJPMF. WJPMF significantly improved pain behaviors in SNI rats by regulating ATP-binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor gamma (PPARG), and superoxide dismutase 2 (SOD2) expression, which were key targets involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. WJPMF shows promising therapeutic potential for NP through the modulation of specific targets, offering a novel therapeutic strategy for managing NP.

Histiocytic necrotizing lymphadenitis with hemophagocytic lymphohistiocytosis in adults: A single-center analysis of 5 cases.

BACKGROUND: Histiocytic necrotizing lymphadenitis (HNL) is a self-limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL-HLH). HNL-HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH. METHODS: We collected the clinical data of patients with HNL-HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected. RESULTS: In this study, we reported five adult patients with HNL-HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow-up. CONCLUSIONS: Our study demonstrated that adult patients with HNL-HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.

Reprimo (RPRM) mediates neuronal ferroptosis via CREB-Nrf2/SCD1 pathways in radiation-induced brain injury.

Neuronal ferroptosis has been found to contribute to degenerative brain disorders and traumatic and hemorrhagic brain injury, but whether radiation-induced brain injury (RIBI), a critical deleterious effect of cranial radiation therapy for primary and metastatic brain tumors, involves neuronal ferroptosis remains unclear. We have recently discovered that deletion of reprimo (RPRM), a tumor suppressor gene, ameliorates RIBI, in which its protective effect on neurons is one of the underlying mechanisms. In this study, we found that whole brain irradiation (WBI) induced ferroptosis in mouse brain, manifesting as alterations in mitochondrial morphology, iron accumulation, lipid peroxidation and a dramatic reduction in glutathione peroxidase 4 (GPX4) level. Moreover, the hippocampal ferroptosis induced by ionizing irradiation (IR) mainly happened in neurons. Intriguingly, RPRM deletion protected the brain and primary neurons against IR-induced ferroptosis. Mechanistically, RPRM deletion prevented iron accumulation by reversing the significant increase in the expression of iron storage protein ferritin heavy chain (Fth), ferritin light chain (Ftl) and iron importer transferrin receptor 1 (Tfr1), as well as enhancing the expression of iron exporter ferroportin (Fpn) after IR. RPRM deletion also inhibited lipid peroxidation by abolishing the reduction of GPX4 and stearoyl coenzyme A desaturase-1 (SCD1) induced by IR. Importantly, RPRM deletion restored or even increased the expression of nuclear factor, erythroid 2 like 2 (Nrf2) in irradiated neurons. On top of that, compromised cyclic AMP response element (CRE)-binding protein (CREB) signaling was found to be responsible for the down-regulation of Nrf2 and SCD1 after irradiation, specifically, RPRM bound to CREB and promoted its degradation after IR, leading to a reduction of CREB protein level, which in turn down-regulated Nrf2 and SCD1. Thus, RPRM deletion recovered Nrf2 and SCD1 through its impact on CREB. Taken together, neuronal ferroptosis is involved in RIBI, RPRM deletion prevents IR-induced neuronal ferroptosis through restoring CREB-Nrf2/SCD1 pathways.

The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients.

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8.73 mg/L were older and had a more advanced stage, lower levels of platelets, albumin, and fibrinogen, and higher creatinine level. The serum B2M >8.73 mg/L, creatinine ≥133 µmol/L, fibrinogen ≤1.5 g/L, agranulocytosis (<0.5 × 109/L), severe thrombocytopenia (<50 × 109/L), and high Epstein-Barr virus DNA copy number were found to have independent prognostic values in all patients, and the serum B2M >8.73 mg/L was also an independent prognostic factor in patients with creatinine <133 µmol/L. Finally, a prognostic scoring system was established based on independent prognostic factors of all patients and categorized the patients into three groups with significant prognostic differences. This study confirmed that the serum B2M level can be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.

Gut microbiome as a key monitoring indicator for reintroductions of captive animals.

Reintroduction programs seek to restore degraded populations and reverse biodiversity loss. To examine the hypothesis that gut symbionts could be used as an indicator of reintroduction success, we performed intensive metagenomic monitoring over 10 years to characterize the ecological succession and adaptive evolution of the gut symbionts of captive giant pandas reintroduced to the wild. We collected 63 fecal samples from 3 reintroduced individuals and 22 from 9 wild individuals and used 96 publicly available samples from another 3 captive individuals. By microbial composition analysis, we identified 3 community clusters of the gut microbiome (here termed enterotypes) with interenterotype succession that was closely related to the reintroduction process. Each of the 3 enterotypes was identified based on significant variation in the levels of 1 of 3 genera: Clostridium, Pseudomonas, and Escherichia. The enterotype of captive pandas was Escherichia. This enterotype was gradually replaced by the Clostridium enterotype during the wild-training process, which in turn was replaced by the Pseudomonas enterotype that resembled the enterotype of wild pandas, an indicator of conversion to wildness and a successful reintroduction. We also isolated 1 strain of Pseudomonas protegens from the wild enterotype, a previously reported free-living microbe, and found that its within-host evolution contributed to host dietary adaptation in the wild. Monitoring gut microbial structure provides a novel, noninvasive tool that can be used as an indicator of successful reintroduction of a captive individual to the wild.

Microbiomas intestinales como indicadores clave de monitoreo para la reintroducción de animales cautivos Resumen Los programas de reintroducción buscan restaurar las poblaciones degradadas y revertir la pérdida de la biodiversidad. Realizamos un monitoreo metagenómico intensivo durante más de diez años para caracterizar la sucesión ecológica y la evolución adaptativa de los simbiontes intestinales de pandas reintroducidos en la naturaleza y así comprobar la hipótesis de que estos simbiontes pueden usarse como indicadores de una reintroducción exitosa. Recolectamos 63 muestras fecales de tres individuos reintroducidos y 22 de nueve individuos silvestres y usamos 96 muestras disponibles al público de otros tres individuos cautivos. Mediante el análisis de la composición microbiana identificamos tres grupos comunitarios del microbioma intestinal (denominados como enterotipos) con una sucesión entre enterotipos relacionada cercanamente al proceso de reintroducción. Identificamos cada uno de los tres enterotipos con base en la variación significativa en los niveles de uno de los tres géneros: Clostridium, Pseudomonas, y Escherichia. El enterotipo de los pandas cautivos fue Escherichia. A este enterotipo lo reemplazó gradualmente el enterotipo de Clostridium durante el proceso de adaptación a la naturaleza, y a su vez fue reemplazado por el enterotipo de Pseudomonas similar al de los pandas silvestres, un indicador de la conversión a la vida silvestre y de una reintroducción exitosa. También aislamos una cepa de Pseudomonas protegens del enterotipo silvestre, un microbio reportado previamente como de vida libre, y descubrimos que su evolución dentro del hospedero contribuyó a que este se adaptara a la naturaleza de la dieta. El monitoreo de la estructura microbiana intestinal proporciona una herramienta novedosa y no invasiva que puede usarse como indicador del éxito de la reintroducción de un individuo cautivo a la naturaleza.

Targeting the cGAS-STING Pathway Inhibits Peripheral T-cell Lymphoma Progression and Enhances the Chemotherapeutic Efficacy.

Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous group of mature T-cell malignancies. The efficacy of current first-line treatment is dismal, and novel agents are urgently needed to improve patient outcomes. A close association between the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and tumor promotion exists, revealing prospective therapeutic targets. This study, investigates the role of the cGAS-STING pathway and its underlying mechanisms in PTCL progression. Single-cell RNA sequencing showes that the cGAS-STING pathway is highly expressed and closely associated with PTCL proliferation. cGAS inhibition suppresses tumor growth and impaires DNA damage repair. Moreover, Cdc2-like kinase 1 (CLK1) is critical for residual tumor cell survival after treatment with cGAS inhibitors, and CLK1 suppression enhances sensitivity to cGAS inhibitors. Single-cell dynamic transcriptomic analysis indicates reduced proliferation-associated nascent RNAs as the underlying mechanism. In first-line therapy, chemotherapy-triggered DNA damage activates the cGAS-STING pathway, and cGAS inhibitors can synergize with chemotherapeutic agents to kill tumors. The cGAS-STING pathway is oncogenic in PTCL, whereas targeting cGAS suppresses tumor growth, and CLK1 may be a sensitivity indicator for cGAS inhibitors. These findings provide a theoretical foundation for optimizing therapeutic strategies for PTCL, especially in patients with relapsed/refractory disease.

Reprimo (RPRM) as a Potential Preventive and Therapeutic Target for Radiation-Induced Brain Injury via Multiple Mechanisms.

Patients receiving cranial radiotherapy for primary and metastatic brain tumors may experience radiation-induced brain injury (RIBI). Thus far, there has been a lack of effective preventive and therapeutic strategies for RIBI. Due to its complicated underlying pathogenic mechanisms, it is rather difficult to develop a single approach to target them simultaneously. We have recently reported that Reprimo (RPRM), a tumor suppressor gene, is a critical player in DNA damage repair, and RPRM deletion significantly confers radioresistance to mice. Herein, by using an RPRM knockout (KO) mouse model established in our laboratory, we found that RPRM deletion alleviated RIBI in mice via targeting its multiple underlying mechanisms. Specifically, RPRM knockout significantly reduced hippocampal DNA damage and apoptosis shortly after mice were exposed to whole-brain irradiation (WBI). For the late-delayed effect of WBI, RPRM knockout obviously ameliorated a radiation-induced decline in neurocognitive function and dramatically diminished WBI-induced neurogenesis inhibition. Moreover, RPRM KO mice exhibited a significantly lower level of acute and chronic inflammation response and microglial activation than wild-type (WT) mice post-WBI. Finally, we uncovered that RPRM knockout not only protected microglia against radiation-induced damage, thus preventing microglial activation, but also protected neurons and decreased the induction of CCL2 in neurons after irradiation, in turn attenuating the activation of microglial cells nearby through paracrine CCL2. Taken together, our results indicate that RPRM plays a crucial role in the occurrence of RIBI, suggesting that RPRM may serve as a novel potential target for the prevention and treatment of RIBI.

Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance.

HS6ST2 has ability to encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS and a crucial regulator of cell growth, differentiation, adhesion, and migration. Although mounting evidence supports a vital role for HS6ST2 in tumorigenesis of some cancers, no pan-cancer analysis of HS6ST2 has been reported. Therefore, we aimed to explore the prognostic value of HS6ST2 in 33 cancer types and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Lines Encyclopedia, Genotype Tissue Expression, and GSCA, we used a range of bioinformatics approaches to explore the potential carcinogenic role of HS6ST2, analysis of HS6ST2 and prognosis, DNA methylation, RNA methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and immune cell infiltration in different tumors. The results show that HS6ST2 was highly expressed in most cancers but lower in Breast invasive carcinoma, Kidney Chromophobe, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Uterine Corpus Endometrial Carcinoma. Moreover, HS6ST2 is positively or negatively associated with prognosis in different cancers. HS6ST2 expression was not only associated with MSI in 5 cancer types and associated with TMB in 10 cancer types, and it's significantly correlated with DNA methylation in 13 types of cancer, but it's correlated with RNA methylation related genes in most cancer. HS6ST2 expression was correlated with immune cell infiltration, immune-related genes, tumor immune microenvironment, and drug resistance in various cancers. Eventually, HS6ST2 was validated in human lung adenocarcinoma tissues. Our study reveals that HS6ST2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

PandaGUT provides new insights into bacterial diversity, function, and resistome landscapes with implications for conservation.

BACKGROUND: The gut microbiota play important roles in host adaptation and evolution, but are understudied in natural population of wild mammals. To address host adaptive evolution and improve conservation efforts of threatened mammals from a metagenomic perspective, we established a high-quality gut microbiome catalog of the giant panda (pandaGUT) to resolve the microbiome diversity, functional, and resistome landscapes using approximately 7 Tbp of long- and short-read sequencing data from 439 stool samples. RESULTS: The pandaGUT catalog comprises 820 metagenome-assembled genomes, including 40 complete closed genomes, and 64.5% of which belong to species that have not been previously reported, greatly expanding the coverage of most prokaryotic lineages. The catalog contains 2.37 million unique genes, with 74.8% possessing complete open read frames, facilitating future mining of microbial functional potential. We identified three microbial enterotypes across wild and captive panda populations characterized by Clostridium, Pseudomonas, and Escherichia, respectively. We found that wild pandas exhibited host genetic-specific microbial structures and functions, suggesting host-gut microbiota phylosymbiosis, while the captive cohorts encoded more multi-drug resistance genes. CONCLUSIONS: Our study provides largely untapped resources for biochemical and biotechnological applications as well as potential intervention avenues via the rational manipulation of microbial diversity and reducing antibiotic usage for future conservation management of wildlife. Video Abstract.

Single-cell RNA sequencing in double-hit lymphoma: IMPDH2 induces the progression of lymphoma by activating the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: IMPDH2 is the rate-limiting enzyme of the de novo GTP synthesis pathway and has a key role in tumors; however, the specific mechanism underlying IMPDH2 activity in diffuse large B cell lymphoma (DLBCL) is still undetermined. This study aims to explore the potential mechanism of IMPDH2 in DLBCL, and its possible involvement in double-hit lymphoma (DHL), i.e., cases with translocations involving MYC and BCL2 and/or BCL6. METHODS: Using single-cell sequencing and bioinformatics analysis to screen for IMPDH2. Exploring the differential expression of IMPDH2 and its correlation with prognosis through multiplexed immunofluorescence analysis. Using CCK8, EdU, clone formation assay, and animal model to analyze biological behavior changes after inhibiting IMPDH2. Explaining the potential mechanism of IMPDH2 in DLBCL by Western blot and multiplexed immunofluorescence. RESULTS: Prognostic risk model was constructed by single-cell sequencing, which identified IMPDH2 as a DHL-related gene. IMPDH2 was highly expressed in cell lines and tissues, associated with poor patient prognosis and an independent prognostic factor. In vitro and in vivo experiments showed that IMPDH2 inhibition significantly inhibited DHL cell proliferation. Flow cytometry showed apoptosis and cycle arrest. Western blot results suggested that c-Myc regulated the activation of PI3K/AKT/mTOR signaling pathway by IMPDH2 to promote tumor development in DHL. Moreover, multiplex immunofluorescence revealed decreased T-cell infiltration within the tumor microenvironment exhibiting concurrent high expression of IMPDH2 and PD-L1. CONCLUSIONS: Our results suggest that IMPDH2 functions as a tumor-promoting factor in DHL. This finding is expected to generate novel insights into the pathogenesis of these patients, thereby identifying potential therapeutic targets.

Exploring the nexus of green finance and renewable energy consumption: unraveling synergistic effects and spatial spillovers.

As China transitions towards a green and low-carbon energy system, it is crucial to have the support of green finance. In this study, we explore the effects of synergy and spatial spillovers in the development of green finance and the consumption of renewable energy. By taking a synergistic perspective, we aim to provide new insights for energy structure reform. We use a spatial simultaneous equations model in combination with a three-stage generalized spatial least squares approach, our findings are the following: firstly, there is a positive synergy between the development of green finance and the consumption of renewable energy. Secondly, there are positive spatial spillovers in the development of green finance and the consumption of renewable energy, but the regional interaction effects of green finance development on renewable energy consumption are negative. Furthermore, we observe that the impact of renewable energy consumption on green finance development has been increasing since 2013. However, the reverse relationship is not true, indicating that the renewable energy industry has stabilized and is gaining appeal in financial markets. Our study highlights that the development of green finance can promote an increase in renewable energy consumption through the facilitation of economic growth, green technology innovation, and the upgrading of the industrial structure. We emphasize the importance of regional and industrial coordination to create synergy between green finance development and renewable energy consumption.

Case report: Immune modulation after PD-1 inhibitor therapy in a patient with extranodal NK/T-cell lymphoma secondary to chronic active Epstein-Barr virus disease unveiled by single-cell transcriptomics.

Chronic active Epstein-Barr virus disease (CAEBV) is a systemic lymphoproliferative disorder that is closely linked to Epstein-Barr virus (EBV) infection. The clinical course and severity of CAEBV can vary, and in some cases, it can progress to overt lymphoma, which is characterized by extranodal natural killer/T-cell lymphoma (ENKTL) and has a poor clinical outcome. Although anti-programmed cell death protein-1 (PD-1) therapy has shown effectiveness in some patients with EBV-associated disease, it has been less successful in others, and the exact mechanism of action of PD-1 inhibitor therapy in these diseases remains unclear. In this report, we describe a patient who was diagnosed with ENKTL secondary to CAEBV and experienced rapid disease progression accompanied by hyperinflammation after receiving PD-1 inhibitor therapy. Single-cell RNA sequencing revealed a significant increase in the patient's lymphocyte count, especially in natural killer cells, with increased activity following PD-1 inhibitor therapy. This case raises questions about the efficacy and safety of PD-1 inhibitor therapy in patients with EBV-associated diseases.

A Rare B-Myeloid Conversion of Follicular Lymphoma into Clonally Related Acute Myeloid Leukemia: A Case Report.

Follicular lymphoma (FL) is a highly prevalent indolent lymphoma, and the risk of histological transformation is approximately 2-3% per year. Transformation of FL generally occurs in the same lineage (B cell lineage). Another rare form of disease progression is the transformation of neoplastic B-cells to another cell lineage such as acute myeloid leukemia (AML). The low incidence of B-myeloid transformation associated with poor prognosis hinders the establishment of model systems to identify molecular mechanisms. A 64-year-old woman was diagnosed with FL and achieved a satisfactory response after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Approximately one month after treatment terminated, the disease progressed to AML with an increased white blood cell count and abnormal coagulation. Interestingly, nucleotide sequence analysis of the genomic region encoding the immunoglobulin heavy-chain variable domain showed the possibility of homologous transformation from lymphoma to leukemia cells. Although the patient experienced transient improvement after undergoing treatment with one cycle of idarubicin and cytarabine combined with etoposide, she relapsed and died 8 days after venetoclax salvage therapy. Patient with B-myeloid transformation was associated with an aggressive clinical course and poor prognosis. Conventional strategies for treating histologically transformed AML were ineffective. However, treatment with a Bcl-2 inhibitor could serve as an option. Here we review the literature relevant to this rare histological transformation of FL.