Sensitive organic/inorganic polarized photodetectors enhanced by charge transfer with image sensing capacity.

Organic photodetectors (OPDs) have attracted increasing attention in the future wearable sensing and real-time health monitoring, due to their intrinsic features including the mechanical flexibility, low-cost processing and cooling-free operations; while their performances are lagging as the results of inferior carrier mobility and small exciton diffusion coefficient of organic molecules. Graphene exhibits the great photoresponse with wide spectral bandwidth and high response speed. However, weak light absorption and the absence of a gain mechanism have limited its photoresponsivity. Here, we report a sensitive organic/inorganic phototransistor with fast response speed by coupling PTCDA organic single crystal with the monolayer graphene. The long range exciton diffusion in highly ordered π-conjugated molecules, efficient exciton dissociation and charge transfer at the PTCDA/graphene heterointerfaces, and the high mobility of graphene enable a high responsivity (8 × 104A/W), short response time (220 µs) and excellent specific detectivity (>1011 Jones), which is higher than the level of commercial on-chip device. This interfacial photogating effect is verified by the high-resolution spatial photocurrent mapping experiment. In addition, the high sensitivity to polarization is clear and the ultrahigh photoconductive gain enables a near-infrared (NIR) response for 980 and 1550 nm. Finally, high-speed visible and NIR imaging applications are successfully demonstrated. This work suggests that high quality organic single crystal/graphene is a promising platform for future high performance optoelectronic systems and imaging applications.

Venetoclax plus dose-adjusted R-EPOCH (VR-DA-EPOCH) or G-EPOCH bridging to subsequent cellular therapy for the patients with transformed lymphoma a single center clinical experience.

Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4-29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.

The Clinical Significance and Prognostic Role of Whole-Blood Epstein-Barr Virus DNA in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis.

PURPOSE: To evaluate the role of circulating Epstein-Barr virus (EBV) DNA in lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). METHODS: We conducted a retrospective cohort study to explore the clinical and prognostic significance of EBV DNA in lymphoma-associated HLH. We included adult patients with combined diagnoses of lymphoma and HLH from January 2010 and November 2022 by retrieving the medical record system. RESULTS: A total of 281 patients with lymphoma-associated HLH were identified. Elevated whole-blood EBV DNA was observed in 54.4% (153/281) of patients, and the median copy number was significantly higher in the T/NK-cell malignancies (199,500, interquartile range, 30,000-1,390,000) than that in the B-cell non-Hodgkin lymphoma (5520, interquartile range, 1240-28,400, P < 0.001). The optimum cutoff for predicting survival was 16,100 copies/mL. Compared to the patients with EBV DNA ≤ 16,100 copies/mL, those with EBV DNA > 16,100 copies/mL were younger and had more T/NK-cell malignancies, lower levels of neutrophils and fibrinogen, and higher levels of hemoglobin, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and ß2-microglobulin. A higher load of EBV DNA (> 16,100 copies/mL), thrombocytopenia (< 100 × 109/L), neutropenia (< 1 × 109/L), hypofibrinogenemia (≤ 1.5 g/L), and elevated levels of creatinine (> 133 µmol/L) were independent adverse predictors of 60-day overall survival and overall survival. A prognostic index based on EBV DNA and the other four factors was established to categorize the patients into four groups with significantly different outcomes. CONCLUSION: Our study identified high EBV load as a risk factor for lymphoma-associated HLH and established a prognostic index to predict outcomes.

Optical-fiber-integrated high-speed organic phototransistor with broadband imaging capacity.

Fiber optic communication is becoming the central pillar of modern high-speed communication technology, which involves the abundant fiber components. Currently, most of photodetectors are fabricated on the silicon chip, so mass fiber-to-chip interfaces increase the complexity of advanced optoelectronic system, and also grow the risk of optical information loss. Here, we report an all-fiber organic phototransistor by employing rubrene single crystal and few-layer graphene to realize the "plug-to-play" operation. The device shows a broadband photoresponse from the ultraviolet to visible range, with fast response times of approximately 130/170 µs and reasonable specific detectivity of 6 × 109 Jones, which is close to the level of commercial on-chip device. Finally, several imaging applications are successfully demonstrated by deploying this all-fiber device. Our work provided an efficient strategy for fabricating all-fiber organic devices, and confirmed their significant potential in future optical fiber optoelectronics.

Diagnosis, treatment and genetic analysis of an elderly patient with Gaucher's disease characterized by marked multiple bone destruction.

Gaucher's disease is a rare autosomal recessive genetic disease. Due to the decrease or lack of glucocerebrosidase (GBA) activity in lysosome caused by the mutation of GBA gene, its substrate glucocerebroside is detained in lysosome, resulting in clinical manifestations of liver, spleen, kidney, bone, hematopoietic system and even nervous system involvement. Here, we report a case of elderly patient presenting marked multiple bone destruction, with childhood medical history of splenectomy and "osteomyelitis". The patient has a significantly enlarged liver, accompanied by anemia, thrombocytopenia and osteopenia. Laboratory studies show this patient has low blood GBA activity and high glucosyl sphingosine level and increased chitotriosidase activity. Genetic testing revealed a homozygous missense variant NM_001005741.2 c.770A>G (p.Asp257Gly) in the patient's GBA gene. After 6 months of enzyme replacement therapy, the patient's platelets returned to normal, anemia improved, and liver volume decreased. Further detections show that the mother and brothers of the patient have heterozygous mutations at this locus, which is consistent with Mendelian inheritance law. Although this variant has not been reported in literatures or database, both clinical manifestations, characteristics of enzymology and biomarkers, and the effect of enzyme replacement therapy support the diagnosis of Gaucher's disease. The Asp257Gly variant is therefore assessed as a clinical pathogenic variant. This study expands the spectrum of the GBA gene variants. The diagnosis and treatment process of this case also provide reference for the early identification, diagnosis and early treatment of this kind of patients.

Dirac semimetal saturable absorber with actively tunable modulation depth.

In this Letter, we demonstrate an electrically contacted saturable absorber (SA) device based on topological Dirac semimetal Cd3As2. With a current-induced temperature change in the range of 297-336 K, the modulation depth of the device is found to be significantly altered from 33% to 76% (under the irradiation of a 1560 nm femtosecond laser). The broad tuning of the modulation depth is attributed to the strong temperature dependence of the carrier concentration close to room temperature. The simple tuning mechanism uncovered here, together with the compatibility with III-V compounds substrate, such as GaAs, points to the potential of fabricating broadband, electrically tunable, SESAM-like devices based on emerging bulk Dirac materials.

Toward facile broadband photodetectors based on self-assembled ZnO nanobridge/rubrene heterointerface.

ZnO nanowire photodetectors have attracted much attention due to their excellent optoelectronic performance. However, operating speed remains a challenge, and scalability is also impeded by uncontrolled transfer methods and sophisticated fabrication process. In this paper, we have fabricated an excellent ZnO nanobridge ultraviolet photodetector array by using a simple one-step method. The faster photoresponse speed and a broader response wavelength (from UV to visible range) have been achieved by constructing a type-II ZnO/rubrene heterointerface. Performance enhancement is believed to arise from the well-matching band alignment and highly efficient separation of photogenerated electron-hole pairs at the heterointerface. Our strategy provides a simple and promising route to develop cost-effective and highly sensitive UV-vis photodetectors.

Definition of disease-progression risk stratification in untreated chronic lymphocytic leukemia using combined clinical, molecular and virological variables.

Prognoses of persons with chronic lymphocytic leukemia (CLL) including time-to-therapy (TTT) and survival is heterogeneous. Risk factors and predictive scoring systems are mostly developed in persons of predominately European descent with CLL. Whether these systems accurately predict TTT and survival of Han Chinese with CLL is unknown. We interrogated clinical and laboratory data from 334 newly diagnosed, untreated Chinese CLL without treatment indication upon diagnosis to identify variables associated with TTT and develop a prognostic score. Binet stage, blood lymphocyte level, TP53 abnormality, unmutated IGHV, prior HBV, and EBV infections were independently associated with TTT in multivariate analyses. We constructed a prognostic score dividing subjects into cohorts with low, intermediate, and high risk from diagnosis to TTT. Median TTTs were 139 months (range, 85-189 months), 25 months (12-38 months), and 4 months (1-7 months; P-value for trend <0.001). We identified variables associated with TTT in Chinese with CLL with no treatment indication and developed a predictive model for survival. Some variables associated with TTT are similar to those of persons of predominately European descent, whereas others, such as HBV and/or EBV infections, operate in Chinese and Europeans but are not currently included in prognostic and predictive staging systems in persons of European descent. They should be investigated.

A higher percentage of cells with 13q deletion predicts worse outcome in Chinese patients with chronic lymphocytic leukemia carrying isolated 13q deletion.

Previous studies showed that, in chronic lymphocytic leukemia (CLL) patients with isolated 13q deletion (13q-), those carrying higher percentage of leukemic cells with 13q- had more aggressive diseases. However, the prognostic value of the percentage of leukemic cells with 13q- in Chinese CLL patients with isolated 13q- remained to be determined. Using interphase fluorescence in situ hybridization (FISH), we identified 82 patients (25.4%) with isolated 13q deletion from a cohort of 323 untreated CLL patients. Among patients with isolated 13q deletion, cases of 13q- cells ≥ 80% (13q-H) had significantly shorter time to first treatment (TTT) than those of < 80% 13q- cells (13q-L) (median 11 vs. 92 months, p = 0.0016). A higher lymphocyte count (p = 0.0650) was associated with 13q-H, while other clinical, immunophenotypic, or molecular features did not differ between patients with 13q-H and 13q-L. Although 13q-H only showed marginal significance in multivariate analysis of TTT (hazards ratio 2.007; 95% confidence interval 0.975-4.129; p = 0.059), it helped refine the risk stratification based on Binet stage or immunoglobulin heavy chain variable gene (IGHV) status. In cases in Binet A or B stage, patients with 13q-H had a significantly shorter TTT (median TTT 18 months vs. undefined, p = 0.0101). And in IGHV mutated patients, 13q-H was also associated with reduced TTT (median TTT 13q-H. 18 months vs. 13q-L undefined, p = 0.0163). In conclusion, the prognosis of CLL patients with isolated 13q deletion was heterogeneous with 13q-H identifying patients with worse outcome.

Low absolute CD4+ T cell counts in peripheral blood are associated with inferior survival in follicular lymphoma.

Host immunity and tumor microenvironment significantly influence follicular lymphoma (FL) outcomes. Lymphopenia has been identified as a negative prognostic factor for FL. However, there is limited data regarding prognostic value of peripheral blood T lymphocyte subsets, especially absolute CD4+ T cell counts (ACD4C) in FL. We studied 127 consecutive FL patients to investigate whether peripheral blood ACD4C or absolute monocytes (AMC) at diagnosis had an impact on FL prognosis. In our cohort, both low ACD4C and high AMC were the parameters associated with inferior progression-free survival (PFS) (P = 0.021 and P = 0.013, respectively) and inferior overall survival (OS) (P = 0.020 and P = 0.005, respectively) by univariate analysis. Multivariate analysis revealed that only low ACD4C was statistically significant in worse PFS (hazard ratio, 2.811; 95 % confidence interval, 1.137-6.950; P = 0.025) and shorter OS (hazard ratio, 3.393; 95 % confidence interval, 1.037-11.105; P = 0.043) independent of FLIPI-2. Evaluation of blood ACD4C could be a useful indicator of outcome in previously untreated FL patients.

Organic-Inorganic Rubrene/WS2 Heterostructure for Broadband Detection and Polarization Imaging.

Organic single crystals exhibit improved carrier mobility, longer exciton diffusion length, anisotropic charge transport, and unique linear dichroism, while its high exciton binding energy seriously limits the free-carrier generation and photoelectric conversion efficiency. Layered van der Waals heterostructures, which integrate organic crystals with high mobility two-dimensional (2D) inorganic semiconductors, are promising for promoting exciton dissociation and boosting sensitivity by utilizing the interfacial potential and photogating effect. In this work, organic single-crystal rubrene is integrated with a few-layer WS2 to design the high-performance photodetector. The device exhibits an excellent responsivity of 1000 A W-1, and a fast speed of 180 µs, which is far superior to the individual WS2 device. Equally importantly, this device provides excellent polarization detection performance by virtue of the anisotropic properties of rubrene, and the dichroic ratios are 1.56, 1.5, and 1.7 for 375, 405, and 658 nm irradiation, respectively. Finally, several high-resolution single-pixel broadband polarization imaging was demonstrated. Our work shows that organic-inorganic heterostructure is an essential candidate for improving optoelectronics performance and has potential for polarization imaging.

Asymmetric Schottky Barrier in Rubrene Transistor via Monolayer Graphene Insertion toward Self-Powered Imaging.

Organic semiconductor materials featuring lightweight, and flexibility may play a significant role in various future applications, such as foldable displays, wearable devices, and artificial skin. For developing high-performance organic devices, organic crystals are highly desired, while a remaining fundamental issue is their contact problem. Here, we have grown a high-quality rubrene single crystal by utilizing a simple in-air sublimation technique. The contact characteristics (barrier height and contact resistance) are detail-studied by resist-free transfer electrodes (Au metal or graphene/Au). The Schottky barrier of the rubrene/graphene interface is lower and can be also modulated by gate bias, which is confirmed by spatial photocurrent mapping. Finally, we demonstrated the zero-bias photocurrent imaging application by constructing the asymmetrical device employing different electrode contacts. Our work would be of significance for studying the contact issue of organic crystals and wireless imaging.

Case report: Identification of atypical mantle cell lymphoma with CCND3 rearrangement by next-generation sequencing.

The t(11;14) (q13;q32) translocation resulting in overexpression of cyclin D1 is the major oncogenic mechanism in mantle cell lymphoma (MCL). Most MCLs can be diagnosed based on morphological features, cyclin D1 expression, and IGH/CCND1 rearrangement. However, in some atypical cases where conventional FISH studies fail to detect IGH/CCND1 rearrangement or immunohistochemistry for cyclin D1 is negative, the diagnosis of the disease can be difficult. Hence, next-generation sequencing (NGS) may allow the identification of molecular alterations and assist in the diagnosis of atypical MCL. In this study, we reported a case of a patient diagnosed as asymptomatic MCL who presented with lymphadenopathy during the initial assessment. A lymph node biopsy was performed and the results revealed a high Ki67 index. However, initial diagnosis of aggressive MCL was difficult since the IGH/CCND1 rearrangement result was negative. Ultimately, by the aid of NGS we identified a rare CCND3 rearrangement in the patient, which lead to overexpression of cyclin D3, thereby facilitating the diagnosis of MCL.

Gate Controlled Photocurrent Generation Mechanism in Air-Grown Organic Single Crystals for High-Speed Multiband Imaging.

Organic semiconductors herald new opportunities for fabricating high-performance flexible and wearable optoelectronic devices owing to their intrinsic mechanical flexibility, excellent optical absorption, and cool-free operation. The photocurrent generation mechanisms are of multiple physical origins, including photoconductive, photovoltaic, and photogating effects, and the influence of individual effects on the device figures-of-merit is still not well understood. Here we fabricated a high-performance pentacene single-crystal transistor employing graphene electrodes and demonstrated the modulation from the photogating mechanism to the photoconduction effect by controlling gate bias. Control experiments indicate that the calculation based on transfer curves tends to overestimate the responsivity due to nearby trap states. Using a high frequency-modulated light signal to suppress the trapping process, we successfully measured its intrinsic -3 dB bandwidth of 75 kHz. Finally, high-resolution and UV-NIR high-speed imaging capability was demonstrated. Our work provides new guidelines for understanding the photophysical process and intrinsic performances of organic devices and also confirms the potential of organic single crystals in high-speed imaging applications.

Prognostic value and therapeutic targeting of XPO1 in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a subtype of B-cell malignancy with high heterogeneity. XPO1 is highly expressed in many hematological malignancies, which predicts poor prognosis. In the study, we aimed to explore the prognostic role of XPO1 and the therapeutic effect of Selinexor, a selective inhibitor of nuclear export, which targets XPO1. We collected 200 CLL samples in our center to confirm XPO1 mRNA expression and analyzed the correlation between XPO1 expression and prognosis. Then, we decreased XPO1 expression with Selinexor to explore the effect of proliferation inhibition, cell cycle arrest, and apoptosis in CLL cell lines. RNA-Seq was performed to explore potential mechanisms. We analyzed XPO1 expression in a cohort of 150 treatment naive patients and another cohort of 50 relapsed and refractory (R/R) patients and found that XPO1 expression was upregulated in 76% of CLL patients compared with healthy donors. Survival analysis suggested that patients with increased XPO1 expression had inferior treatment-free survival (P = 0.022) and overall survival (P = 0.032). The inhibitor of XPO1, Selinexor, induced apoptosis in primary CLL cells. We showed the effects of Selinexor on proliferation inhibition, cell cycle arrest, and apoptosis in CLL cell lines with JVM3, MEC1, and ibrutinib-resistant (MR) cells via nuclear retention of cargo proteins of IκBα, p65, p50, and FOXO3a. Moreover, downregulation of the NF-κB and FOXO pathways was a common feature of the three CLL cell lines responding to Selinexor, indicating the potential application of XPO1 inhibitor even in the high-risk CLL cells. We identified XPO1 as an unfavorable prognostic factor for CLL patients and provided a rationale for further investigation of the clinically XPO1 targeted therapeutic strategy against CLL.

Discovery of Type II Interlayer Trions.

In terms of interlayer trions, electronic excitations in van der Waals heterostructures (vdWHs) can be classified into Type I (i.e., two identical charges in the same layer) and Type II (i.e., two identical charges in the different layers). Type I interlayer trions are investigated theoretically and experimentally. By contrast, Type II interlayer trions remain elusive in vdWHs, due to inadequate free charges, unsuitable band alignment, reduced Coulomb interactions, poor interface quality, etc. Here, the first observation of Type II interlayer trions is reported by exploring band alignments and choosing an atomically thin organic-inorganic system-monolayer WSe2 /bilayer pentacene heterostructure (1L + 2L HS). Both positive and negative Type II interlayer trions are electrically tuned and observed via PL spectroscopy. In particular, Type II interlayer trions exhibit in-plane anisotropic emission, possibly caused by their unique spatial structure and anisotropic charge interactions, which is highly correlated with the transition dipole moment of pentacene. The results pave the way to develop excitonic devices and all-optical circuits using atomically thin organic-inorganic bilayers.

Boosting the Sensitivity of WSe2 Phototransistor via Janus Interfaces with 2D Perovskite and Ferroelectric Layers.

Hybrid systems have recently attracted increasing attention, which combine the special attributes of each constitute and create interesting functionalities through multiple heterointerface interactions. Here, we design a two-dimensional (2D) hybrid phototransistor utilizing Janus-interface engineering, in which the WSe2 channel combines light-sensitive perovskite and spontaneously polarized ferroelectrics, achieving collective ultrasensitive detection performance. The top perovskite (BA2(MA)3Pb4I13) layer can absorb the light efficiently and provide generous photoexcited holes to WSe2. WSe2 exhibit p-type semiconducting states of different degrees due to the selective light-operated doping effect, which also enables the ultrahigh photocurrent of the device. The bottom ferroelectric (Hf0.5Zr0.5O2) layer dramatically decreases the dark current, which should be attributed to the ferroelectric polarization assisted charge trapping effect and improved gate control. As a whole, our phototransistors show excellent photoelectric performances across the ultraviolet to near-infrared range (360-1050 nm), including an ultrahigh ON/OFF current ratio > 109 and low noise-equivalent power of 1.3 fW/Hz1/2, all of which are highly competitive in 2D semiconductor-based optoelectronic devices. In particular, the devices show excellent weak light detection ability, where the distinguishable photoswitching signal is obtained even under a record-low light intensity down to 1.6 nW/cm2, while showing a high responsivity of 2.3 × 105 A/W and a specific detectivity of 4.1 × 1014 Jones. Our work demonstrates that Janus-interface design makes the upper and lower interfaces complement each other for the joint advancement into high-performance optoelectronic applications, providing a picture to realize the integrated engineering on carrier dynamics by light irradiation, electric field, interfacial trapping, and band alignment.

Exploring the significance of PAK1 through chromosome conformation signatures in ibrutinib-resistant chronic lymphocytic leukaemia.

Ibrutinib exerts promising anticancer effects in chronic lymphocytic leukaemia (CLL). However, acquired resistance occurs during treatment, necessitating the exploration of underlying mechanisms. Although three-dimensional genome organization has been identified as a major player in the development and progression of cancer, including drug resistance, little is known regarding its role in CLL. Therefore, we investigated the molecular mechanisms underlying ibrutinib resistance through multi-omics analysis, including high-throughput chromosome conformation capture (Hi-C) technology. We demonstrated that the therapeutic response to ibrutinib is associated with the expression of p21-activated kinase 1 (PAK1). PAK1, which was up-regulated in CLL and associated with patients' survival, was involved in cell proliferation, glycolysis and oxidative phosphorylation. Furthermore, the PAK1 inhibitor IPA-3 exerted an anti-tumour effect and its combination with ibrutinib exhibited a synergistic effect in ibrutinib-sensitive and -resistant cells. These findings suggest the oncogenic role of PAK1 in CLL progression and drug resistance, highlighting PAK1 as a potential diagnostic marker and therapeutic target in CLL including ibrutinib-resistant CLL.

The pyroptosis-related gene signature predicts prognosis and indicates the immune microenvironment status of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world with great heterogeneity. Pyroptosis has recently been recognized as an inflammatory form of programmed cell death (PCD) and shares a close relationship with apoptosis. Although the role of apoptosis in CLL was comprehensively studied and successfully applied in clinical treatment, the relationship between pyroptosis genes and CLL remained largely unknown. In this study, eight differentially expressed pyroptosis-related genes (PRGs) were identified between CLL and normal B cells. In order to screen out the prognostic value of differentially expressed PRGs, univariate and multivariate Cox regression analyses were conducted and a risk model with three PRG signatures (GSDME, NLRP3, and PLCG1) was constructed. All CLL samples were stratified into high- and low-risk subgroups according to risk scores. The risk model showed high efficacy in predicting both overall survival (OS) and time to first treatment (TTFT). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) showed the dysregulation of immune and inflammatory response in the high-risk group. Single-sample GSEA (ssGSEA) of immune cell infiltration and the activity of immune-related pathways also displayed decreased antitumor immunity in the high-risk group. In conclusion, PRGs are of prognostic value in CLL and may play important roles in tumor immunity, and the underlying relationship between PRGs and CLL needs to be explored further.

CircRIC8B regulates the lipid metabolism of chronic lymphocytic leukemia through miR199b-5p/LPL axis.

OBJECTIVE: Circular RNAs (circRNAs) play a critical role in the modulation of tumor metabolism. However, the expression patterns and metabolic function of circRNAs in chronic lymphocytic leukemia (CLL) remain largely unknown. This study aimed to elucidate the role of circRNAs in the lipid metabolism of CLL. METHODS: The expression and metabolic patterns of circRNAs in a cohort of 53 patients with CLL were investigated using whole transcriptome sequencing. Cell viability, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, lipid analysis, Nile red staining as well as triglyceride (TG) assay were used to evaluate the biological function of circRIC8B in CLL. The regulatory mechanisms of circRIC8B/miR-199b-5p/lipoprotein lipase (LPL) axis were explored by luciferase assay, RNA immunoprecipitation (RIP), qRT-PCR, and fluorescence in situ hybridization (FISH). CCK-8 and flow cytometry were used to verify the inhibition role of cholesterol absorption inhibitor, ezetimibe, in CLL cells. RESULTS: Increased circRIC8B expression was positively correlated with advanced progression and poor prognosis. Knockdown of circRIC8B significantly suppressed the proliferation and lipid accumulation of CLL cells. In contrast, the upregulation of circRIC8B exerted opposite effects. Mechanistically, circRIC8B acted as a sponge of miR-199b-5p and prevented it from decreasing the level of LPL mRNA, and this promotes lipid metabolism alteration and facilitates the progression of CLL. What's more, ezetimibe suppressed the expression of LPL mRNA and inhibited the growth of CLL cells. CONCLUSIONS: In this study, the expressional and metabolic patterns of circRNAs in CLL was illustrated for the 1st time. Our findings revealed that circRIC8B regulates the lipid metabolism abnormalities in and development of CLL through the miR-199b-5p/LPL axis. CircRIC8B may serve as a promising prognostic marker and therapeutic target, which enhances the sensitivity to ezetimibe in CLL.