Screening of genes characteristic of pancreatic cancer by LASSO regression combined with support vector machine and recursive feature elimination, and immune correlation analysis.

BACKGROUND: Pancreatic cancer is a malignant tumor of the digestive tract that shows increased mortality, recurrence, and morbidity year on year. METHODS: Differentially expressed genes between pancreatic cancer and healthy tissues were first analyzed from four datasets within the Gene Expression Omnibus (GEO). Gene ontology, disease ontology, and gene set enrichment analysis of differentially expressed genes were performed, and genes identified as characteristic of pancreatic cancer were screened using LASSO regression combined with support vector machine and recursive feature elimination (SVM-RFE). Differential analysis and receiver operating characteristic curve analysis were performed on the identified eigengenes, and validation was carried out using another dataset from the GEO database. Differences and correlations between characteristic pancreatic cancer genes and immune cells were analyzed. RESULTS: A total of 90 differentially expressed genes were identified by screening, and six genes characteristic of pancreatic cancer were obtained by taking the intersection of two characteristic genes identified by machine learning. Immunoassays yielded multiple immune cells associated with pancreatic cancer signature genes. CONCLUSION: The six characteristic genes screened by a combination of LASSO regression and SVM-RFE are potential new biomarkers for the early diagnosis and prognosis of pancreatic cancer, and could be a novel therapeutic target.

Reduced Proteolipid Protein 2 promotes endoplasmic reticulum stress-related apoptosis and increases drug sensitivity in acute myeloid leukemia.

BACKGROUND: The Proteolipid Protein 2 (PLP2), a protein in the Endoplasmic Reticulum (ER) membrane, has been reported to be highly expressed in various tumors. Previous studies have demonstrated that the reduced PLP2 can induce apoptosis and autophagy through ER stress-related pathways, leading to a decreased proliferation and aggressiveness. However, there is no research literature on the role of PLP2 in Acute Myeloid Leukemia (AML). METHODS: PLP2 expression, clinical data, genetic mutations, and karyotype changes from GEO, TCGA, and timer2.0 databases were analyzed through the R packages. The possible functions and pathways of cells were explored through GO, KEGG, and GSEA enrichment analysis using the clusterProfiler R package. Immuno-infiltration analysis was conducted using the Cibersort algorithm and the Xcell R package. RT-PCR and western blot techniques were employed to identify the PLP2 expression, examine the knockdown effects in THP-1 cells, and assess the expression of genes associated with endoplasmic reticulum stress and apoptosis. Flow cytometry was utilized to determine the apoptosis and survival rates of different groups. RESULTS: PLP2 expression was observed in different subsets of AML and other cancers. Enrichment analyses revealed that PLP2 was involved in various tumor-related biological processes, primarily apoptosis and lysosomal functions. Additionally, PLP2 expression showed a strong association with immune cell infiltration, particularly monocytes. In vitro, the knockdown of PLP2 enhanced endoplasmic reticulum stress-related apoptosis and increased drug sensitivity in THP-1 cells. CONCLUSIONS: PLP2 could be a novel therapeutic target in AML, in addition, PLP2 is a potential endoplasmic reticulum stress regulatory gene in AML.

IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.

Chimeric antigen receptor (CAR)-T cell-based therapies demonstrate remarkable efficacy for the treatment of otherwise intractable cancers, particularly B-cell malignancies. However, existing FDA-approved CAR-Ts are limited by low antigen sensitivity, rendering their insufficient targeting to low antigen-expressing cancers. To improve the antigen sensitivity of CAR-Ts, we engineered CARs targeting CD19, CD22, and HER2 by including intrinsically disordered regions (IDRs) that promote signaling condensation. The "IDR CARs" triggered enhanced membrane-proximal signaling in the CAR-T synapse, which led to an increased release of cytotoxic factors, a higher killing activity towards low antigen-expressing cancer cells in vitro, and an improved anti-tumor efficacy in vivo. No elevated tonic signaling was observed in IDR CAR-Ts. Together, we demonstrated IDRs as a new tool set to enhance CAR-T cytotoxicity and to broaden CAR-T's application to low antigen-expressing cancers.

Retinomorphic Motion Detector Fabricated with Organic Infrared Semiconductors.

Organic retinomorphic sensors offer the advantage of in-sensor processing to filter out redundant static backgrounds and are well suited for motion detection. To improve this promising structure, here, the key role of interfacial energetics in promoting charge accumulation to raise the inherent photoresponse of the light-sensitive capacitor is studied. Specifically, incorporating appropriate interfacial layers around the photoactive layer is crucial to extend the carrier lifetime, as confirmed by intensity-modulated photovoltage spectroscopy. Compared to its photodiode counterpart, the retinomorphic sensor shows better detectivity and response speed due to the additional insulating layer, which reduces the dark current and the RC time constant. Lastly, three retinomorphic sensors are integrated into a line array to demonstrate the detection of movement speed and direction, showing the potential of retinomorphic designs for efficient motion tracking.

Biomolecular Condensation of SH2 Domain-Containing Proteins on Membranes.

The plasma membrane serves as an effective platform for signal transduction of membrane receptor pathways. Activation of the T-cell receptor (TCR) triggers the formation of membrane-associated condensates that are formed through liquid-liquid phase separation. These condensates are assembled by multivalent interactions between the tyrosine-phosphorylated receptor/adaptor and the SH2 domain-containing protein at membrane-proximal milieu. Here, we describe a biochemical reconstitution system that has been implemented to decipher the mechanisms of phospholipase PLCγ1-mediated LAT condensate formation. To characterize the interaction between specific phosphotyrosine-SH2 pair, we developed a total internal reflection fluorescence (TIRF) microscopy-based system to quantify the binding preference of each SH2 domain to specific tyrosine in the context of membranes. An assay to determine the condensate-mediated protection of phosphotyrosines from being dephosphorylated by phosphatase is also elaborated. These assays could be applied to study other transmembrane receptor pathway as well as condensates formed on endomembrane systems including the endoplasmic reticulum, mitochondrion, and Golgi apparatus.

Uncooled Mid-Infrared Sensing Enabled by Chip-Integrated Low-Temperature-Grown 2D PdTe2 Dirac Semimetal.

Next-generation mid-infrared (MIR) imaging chips demand free-cooling capability and high-level integration. The rising two-dimensional (2D) semimetals with excellent infrared (IR) photoresponses are compliant with these requirements. However, challenges remain in scalable growth and substrate-dependence for on-chip integration. Here, we demonstrate the inch-level 2D palladium ditelluride (PdTe2) Dirac semimetal using a low-temperature self-stitched epitaxy (SSE) approach. The low formation energy between two precursors facilitates low-temperature multiple-point nucleation (∼300 °C), growing up, and merging, resulting in self-stitching of PdTe2 domains into a continuous film, which is highly compatible with back-end-of-line (BEOL) technology. The uncooled on-chip PdTe2/Si Schottky junction-based photodetector exhibits an ultrabroadband photoresponse of up to 10.6 µm with a large specific detectivity. Furthermore, the highly integrated device array demonstrates high-resolution room-temperature imaging capability, and the device can serve as an optical data receiver for IR optical communication. This study paves the way toward low-temperature growth of 2D semimetals for uncooled MIR sensing.

Wafer-Scale Patterning Synthesis of Two-Dimensional WSe2 Layers by Direct Selenization for Highly Sensitive van der Waals Heterojunction Broadband Photodetectors.

Two-dimensional (2D) transition-metal dichalcogenides (TMDs) exhibit promising potential in fabricating highly sensitive photodetectors due to their unique electrical and optoelectrical characteristics. However, micron-sized 2D materials produced by conventional chemical vapor deposition (CVD) and mechanical exfoliation methods fail to satisfy the demands for applications in integrated optoelectronics and systems given their poor controllability and repeatability. Here, we propose a simple selenization approach to grow wafer-scale (2 in.) 2D p-WSe2 layers with high uniformity and customized patterns. Furthermore, a self-driven broadband photodetector with a p-WSe2/n-Si van der Waals heterojunction has been in situ fabricated with a satisfactory responsivity of 689.8 mA/W and a large specific detectivity of 1.59 × 1013 Jones covering from ultraviolet to short-wave infrared. In addition, a remarkable nanosecond response speed has been recorded under 0.5% duty cycle of the input light. The proposed selenization approach on the growth of 2D WSe2 layers demonstrates an effective route to fabricate highly sensitive broadband photodetectors used for integrated optoelectronic systems.

Phase-controlled van der Waals growth of wafer-scale 2D MoTe2 layers for integrated high-sensitivity broadband infrared photodetection.

Being capable of sensing broadband infrared (IR) light is vitally important for wide-ranging applications from fundamental science to industrial purposes. Two-dimensional (2D) topological semimetals are being extensively explored for broadband IR detection due to their gapless electronic structure and the linear energy dispersion relation. However, the low charge separation efficiency, high noise level, and on-chip integration difficulty of these semimetals significantly hinder their further technological applications. Here, we demonstrate a facile thermal-assisted tellurization route for the van der Waals (vdW) growth of wafer-scale phase-controlled 2D MoTe2 layers. Importantly, the type-II Weyl semimetal 1T'-MoTe2 features a unique orthorhombic lattice structure with a broken inversion symmetry, which ensures efficient carrier transportation and thus reduces the carrier recombination. This characteristic is a key merit for the well-designed 1T'-MoTe2/Si vertical Schottky junction photodetector to achieve excellent performance with an ultrabroadband detection range of up to 10.6 µm and a large room temperature specific detectivity of over 108 Jones in the mid-infrared (MIR) range. Moreover, the large-area synthesis of 2D MoTe2 layers enables the demonstration of high-resolution uncooled MIR imaging capability by using an integrated device array. This work provides a new approach to assembling uncooled IR photodetectors based on 2D materials.

Abnormal linear dichroism transition in two-dimensional PdPS.

The linear dichroism (LD) conversion shows promising applications for polarized detectors, optical transition and light propagation. However, polarity reversal always occurs at a certain wavelength in LD materials, which can only distinguish two wavelength bands as wavelength-selective photodetectors. In this study, the multi-degree-of-freedom of optical anisotropy based on 2D PdPS flakes is carefully described, in which four critical switching wavelengths are observed. Remarkably, the quadruple LD conversion shows a significant wavelength-dependent behavior, allowing us to pinpoint five wavelength bands, 200-239 nm, 239-259 nm, 259-469 nm, 469-546 nm, and 546-700 nm, for a wavelength-selective approach to photodetectors. In addition, the polarized photoresponse under 532 nm was realized with an anisotropy factor of ∼1.51 and further illustrated the in-plane anisotropy. Raman spectroscopy of PdPS flakes also shows strong phonon anisotropy. The unique wavelength-selective property shows great potential for the miniaturization and integration of photodetectors.

Supramolecular copolymerization through self-correction of non-polymerizable transient intermediates.

Kinetic control over structures and functions of complex assembly systems has aroused widespread interest. Understanding the complex pathway and transient intermediates is helpful to decipher how multiple components evolve into complex assemblies. However, for supramolecular polymerizations, thorough and quantitative kinetic analysis is often overlooked. Challenges remain in collecting the information of structure and content of transient intermediates in situ with high temporal and spatial resolution. Here, the unsolved evolution mechanism of a classical self-sorting supramolecular copolymerization system was addressed by employing multidimensional NMR techniques coupled with a microfluidic technique. Unexpected complex pathways were revealed and quantitatively analyzed. A counterintuitive pathway involving polymerization through the 'error-correction' of non-polymerizable transient intermediates was identified. Moreover, a 'non-classical' step-growth polymerization process controlled by the self-sorting mechanism was unraveled based on the kinetic study. Realizing the existence of transient intermediates during self-sorting can encourage the exploitation of this strategy to construct kinetic steady state assembly systems. Moreover, the strategy of coupling a microfluidic technique with various characterization techniques can provide a kinetic analysis toolkit for versatile assembly systems. The combined approach of coupling thermodynamic and kinetic analyses is indispensable for understanding the assembly mechanisms, the rules of emergence, and the engineering of complex assembly systems.

Estrogen Acts Through Estrogen Receptor-ß to Promote Mannan-Induced Psoriasis-Like Skin Inflammation.

Sex-bias is more obvious in several autoimmune disorders, but not in psoriasis. However, estrogen levels fluctuate during puberty, menstrual cycle, pregnancy, and menopause, which are related to variations in psoriasis symptoms observed in female patients. Estrogen has disease promoting or ameliorating functions based on the type of immune responses and tissues involved. To investigate the effects of estrogen on psoriasis, at first, we developed an innate immunity dependent mannan-induced psoriasis model, which showed a clear female preponderance in disease severity in several mouse strains. Next, we investigated the effects of endogenous and exogenous estrogen using ovariectomy and sham operated mice. 17-ß-estradiol (E2) alone promoted the skin inflammation and it also significantly enhanced mannan-induced skin inflammation. We also observed a prominent estrogen receptor-ß (ER-ß) expression in the skin samples, especially on keratinocytes. Subsequently, we confirmed the effects of E2 on psoriasis using ER-ß antagonist (PHTPP) and agonist (DPN). In addition, estrogen was found to affect the expression of certain genes (vgll3 and cebpb), microRNAs (miR146a and miR21), and immune cells (DCs and γδ T cells) as well as chemokines (CCL5 and CXCL10) and cytokines (TNF-α, IL-6, IL-22, IL-23, and IL-17 family), which promoted the skin inflammation. Thus, we demonstrate a pathogenic role for 17-ß-estradiol in promoting skin inflammation, which should be considered while designing new treatment strategies for psoriasis patients.

The effects of combined microwave ablation and open surgery for the treatment of lung cancer-derived thoracolumbar metastases.

OBJECTIVE: To investigate the clinical effects of microwave ablation (MWA) in addition to open surgery for the treatment of lung cancer-derived thoracolumbar metastases. METHODS: This was a single-institution, retrospective, cohort study. From January 2019 to December 2020, a total of 47 patients with lung cancer-derived thoracolumbar metastases underwent posterior spinal canal decompression and fixation surgery in our hospital. Two independent surgical teams treated these patients. One group underwent open surgery combined with MWA therapy, while the other had open surgery only (control). The pre- and post-operative visual analog scale (VAS) scores and the overall survival (OS) were compared between the MWA and control groups. The Frankel Grade classification was applied for the evaluation of the post-surgical spinal cord function. Improvement was defined as an increase of at least one rank from the pre-operative scores. Each patient was evaluated pre- and post-operatively at 48 h, 1 month, and 3-month intervals. Data on surgical-related complications were recorded. RESULTS: Thirty men and 17 women were included, with an average age of 57.9 ± 11.4 years (range, 26-81 years). Twenty-eight patients underwent MWA and were in the MWA group, and 19 patients were included in the control group. Post-operatively all patients were followed up regularly; the median follow-up time was 12 months (range, 3-24 months), and their median OS was 14 months. Patients in the MWA group had a lower VAS score than those in the control group at the 48-h (1.75 ± 1.01 vs 2.47 ± 0.96, P = 0.01) and 1-month (1.79 ± 0.92 vs 2.53 ± 1.35, P = 0.048) check-ups. At the 3-month evaluation, the VAS score differences between the two groups were not significant (P = 0.133). After surgery, spinal cord function improvement was not significantly different between the MWA and control groups (P = 0.515). MWA therapy combined with open surgery was not associated with increased OS compared with the control group (P = 0.492). CONCLUSION: MWA can be an effective and safe pain-relief method but may not extend the OS of patients with lung cancer.

In Situ Fabrication of PdSe2/GaN Schottky Junction for Polarization-Sensitive Ultraviolet Photodetection with High Dichroic Ratio.

Polarization-sensitive ultraviolet (UV) photodetection is of great technological importance for both civilian and military applications. Two-dimensional (2D) group-10 transition-metal dichalcogenides (TMDs), especially palladium diselenide (PdSe2), are promising candidates for polarized photodetection due to their low-symmetric crystal structure. However, the lack of an efficient heterostructure severely restricts their applications in UV-polarized photodetection. Here, we develop a PdSe2/GaN Schottky junction by in situ van der Waals growth for highly polarization-sensitive UV photodetection. Owing to the high-quality junction, the device exhibits an appealing UV detection performance in terms of a large responsivity of 249.9 mA/W, a high specific detectivity, and a fast response speed. More importantly, thanks to the puckered structure of the PdSe2 layer, the device is highly sensitive to polarized UV light with a large dichroic ratio up to 4.5, which is among the highest for 2D TMD material-based UV polarization-sensitive photodetectors. These findings further enable the demonstration of the outstanding polarized UV imaging capability of the Schottky junction, as well as its utility as an optical receiver for secure UV optical communication. Our work offers a strategy to fabricate the PdSe2-based heterostructure for high-performance polarization-sensitive UV photodetection.

Ultrabroadband and High-Detectivity Photodetector Based on WS2/Ge Heterojunction through Defect Engineering and Interface Passivation.

Broadband photodetectors are of great importance for numerous optoelectronic applications. Two-dimensional (2D) tungsten disulfide (WS2), an important family member of transition-metal dichalcogenides (TMDs), has shown great potential for high-sensitivity photodetection due to its extraordinary properties. However, the inherent large bandgap of WS2 and the strong interface recombination impede the actualization of high-sensitivity broadband photodetectors. Here, we demonstrate the fabrication of an ultrabroadband WS2/Ge heterojunction photodetector through defect engineering and interface passivation. Thanks to the narrowed bandgap of WS2 induced by the vacancy defects, the effective surface modification with an ultrathin AlOx layer, and the well-designed vertical n-n heterojunction structure, the WS2/AlOx/Ge photodetector exhibits an excellent device performance in terms of a high responsivity of 634.5 mA/W, a large specific detectivity up to 4.3 × 1011 Jones, and an ultrafast response speed. Significantly, the device possesses an ultrawide spectral response spanning from deep ultraviolet (200 nm) to mid-wave infrared (MWIR) of 4.6 µm, along with a superior MWIR imaging capability at room temperature. The detection range has surpassed the WS2-based photodetectors in previous reports and is among the broadest for TMD-based photodetectors. Our work provides a strategy for the fabrication of high-performance ultrabroadband photodetectors based on 2D TMD materials.

PLCγ1 promotes phase separation of T cell signaling components.

The T cell receptor (TCR) pathway receives, processes, and amplifies the signal from pathogenic antigens to the activation of T cells. Although major components in this pathway have been identified, the knowledge on how individual components cooperate to effectively transduce signals remains limited. Phase separation emerges as a biophysical principle in organizing signaling molecules into liquid-like condensates. Here, we report that phospholipase Cγ1 (PLCγ1) promotes phase separation of LAT, a key adaptor protein in the TCR pathway. PLCγ1 directly cross-links LAT through its two SH2 domains. PLCγ1 also protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK activation and SLP76 phosphorylation. Intriguingly, a nonmonotonic effect of PLCγ1 on LAT clustering was discovered. Computer simulations, based on patchy particles, revealed how the cluster size is regulated by protein compositions. Together, these results define a critical function of PLCγ1 in promoting phase separation of the LAT complex and TCR signal transduction.

Utilization of group 10 2D TMDs-PdSe2 as a nonlinear optical material for obtaining switchable laser pulse generation modes.

In-plane anisotropic two-dimensional (2D) materials have gained considerable interest in the field of research, due to having the potential of being used in different device applications. Recently, among these 2D materials, group 10 transition metal dichalcogenides (TMDs) pentagonal Palladium diselenide (PdSe2) is utilized in various sections of researches like nanoelectronics, thermoelectric, spintronics, optoelectronics, and ultrafast photonics, owing to its high air stability and broad absorption spectrum properties. In this paper, it is demonstrated that by utilizing this novel 2D layered PdSe2 material as a saturable absorber (SA) in an EDF laser system, it is possible to obtain switchable laser pulse generation modes. At first, the Q-switching operation mode is attained at a threshold pump power of 56.8 mW at 1564 nm, where the modulation range of pulse duration and repetition rate is 18.5 µs-2.0 µs and 16.4 kHz-57.0 kHz, respectively. Afterward, the laser pulse generation mode is switched to the mode-locked state at a pump power of 63.1 mW (threshold value) by changing the polarization condition inside the laser cavity, and this phenomenon persists until the maximum pump power of 230.4 mW. For this mode-locking operation, the achieved pulse duration is 766 fs, corresponding to the central wavelength and 3 dB bandwidth of 1566 nm and 4.16 nm, respectively. Finally, it is illustrated that PdSe2 exhibits a modulation depth of 7.01%, which substantiates the high nonlinearity of the material. To the best of the authors' knowledge, this is the first time of switchable modes for laser pulse generation are achieved by using this PdSe2 SA. Therefore, this work will encourage the research community to carry out further studies with this PdSe2 material in the future.

Van der Waals Epitaxial Growth of Mosaic-Like 2D Platinum Ditelluride Layers for Room-Temperature Mid-Infrared Photodetection up to 10.6 µm.

Mid-infrared (MIR) photodetection, covering diverse molecular vibrational regions and atmospheric transmission windows, is vital to civil and military purposes. Versatile use of MIR photodetectors is commonly dominated by HgCdTe alloys, InSb, and quantum superlattices, which are limited by strict operation demands, high-cost, and environmental toxicity. Despite the rapid advances of black phosphorus (BP)-based MIR photodetectors, these are subject to poor stability and large-area integration difficulty. Here, the van der Waals (vdW) epitaxial growth of a wafer-scale 2D platinum ditelluride (PtTe2 ) layer is reported via a simple tellurium-vapor transformation approach. The 2D PtTe2 layer possesses a unique mosaic-like crystal structure consisting of single-crystal domains with highly preferential [001] orientation along the normal direction, reducing the influence of interface defects and ensuring efficient out-of-plane carrier transportation. This characteristic, combined with the wide absorption of PtTe2 and well-designed vertical device architecture, makes the PtTe2 /Si Schottky junction photodetector capable of sensing ultra-broadband light of up to 10.6 µm with a high specific detectivity. Also, the photodetector exhibits an excellent room-temperature infrared-imaging capability. This approach provides a new design concept for high-performance, room-temperature MIR photodetection based on 2D layered materials.

Infrared Nanoimaging of Surface Plasmons in Type-II Dirac Semimetal PtTe2 Nanoribbons.

Topological Dirac semimetals made of two-dimensional transition-metal dichalcogenides (TMDCs) have attracted enormous interest for use in electronic and optoelectronic devices because of their electron transport properties. As van der Waals materials with a strong interlayer interaction, these semimetals are expected to support layer-dependent plasmonic polaritons yet to be revealed experimentally. Here, we demonstrate the apparent retardation and attenuation of mid-infrared (MIR) plasmonic waves in type-II Dirac semimetal platinum tellurium (PtTe2) nanoribbons and nanoflakes by near-field nanoimaging. The attenuated dispersion relations for the plasmonic modes in the PtTe2 nanoribbons (15-25 nm thick) extracted from the near-field standing-wave patterns are applied for the fitting of PtTe2 permittivity in the MIR regime, indicating that both free carriers and Dirac fermions are involved in MIR light-matter interaction in PtTe2. The annihilation of plasmonic modes in the ultrathin (<10 nm) PtTe2 is observed and analyzed, which manifests no near-field resonant pattern due to the intrinsic layer-dependent optoelectronic properties of PtTe2. These results could pave a potential wave for MIR photodetection and modulation with TMDC semimetals.

Multilayered PdSe2/Perovskite Schottky Junction for Fast, Self-Powered, Polarization-Sensitive, Broadband Photodetectors, and Image Sensor Application.

Group-10 transition metal dichalcogenides (TMDs) with distinct optical and tunable electrical properties have exhibited great potential for various optoelectronic applications. Herein, a self-powered photodetector is developed with broadband response ranging from deep ultraviolet to near-infrared by combining FA1- x Cs x PbI3 perovskite with PdSe2 layer, a newly discovered TMDs material. Optoelectronic characterization reveals that the as-assembled PdSe2/perovskite Schottky junction is sensitive to light illumination ranging from 200 to 1550 nm, with the highest sensitivity centered at ≈800 nm. The device also shows a large on/off ratio of ≈104, a high responsivity (R) of 313 mA W-1, a decent specific detectivity (D*) of ≈1013 Jones, and a rapid response speed of 3.5/4 µs. These figures of merit are comparable with or much better than most of the previously reported perovskite detectors. In addition, the PdSe2/perovskite device exhibits obvious sensitivity to polarized light, with a polarization sensitivity of 6.04. Finally, the PdSe2/perovskite detector can readily record five "P," "O," "L," "Y," and "U" images sequentially produced by 808 nm. These results suggest that the present PdSe2/perovskite Schottky junction photodetectors may be useful for assembly of optoelectronic system applications in near future.

B1 oligomerization regulates PML nuclear body biogenesis and leukemogenesis.

ProMyelocyticLeukemia (PML) protein can polymerize into a mega-Dalton nuclear assembly of 0.1-2 µm in diameter. The mechanism of PML nuclear body biogenesis remains elusive. Here, PMLRBCC is successfully purified. The gel filtration and ultracentrifugation analysis suggest a previously unrecognized sequential oligomerization mechanism via PML monomer, dimer, tetramer and N-mer. Consistently, PML B1-box structure (2.0 Å) and SAXS characterization reveal an unexpected networking by W157-, F158- and SD1-interfaces. Structure-based perturbations in these B1 interfaces not only impair oligomerization in vitro but also abolish PML sumoylation and nuclear body biogenesis in HeLaPml-/- cell. More importantly, as demonstrated by in vivo study using transgenic mice, PML-RARα (PR) F158E precludes leukemogenesis. In addition, single cell RNA sequencing analysis shows that B1 oligomerization is an important regulator in PML-RARα-driven transactivation. Altogether, these results not only define a previously unrecognized B1-box oligomerization in PML, but also highlight oligomerization as an important factor in carcinogenesis.