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PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
Additionally, the significant differential expression of CTSB, DPYD, SCARB2, STOM, and GBP1 highlighted their specific roles in the tumorigenesis process.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
In conclusion, this study reveals significant molecular differences between DLBCL subgroups, providing potential biomarkers for risk stratification in DLBCL.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
The findings lay a solid foundation for further mechanistic studies, offering insights into the molecular heterogeneity of DLBCL and potential avenues for future research.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
Future studies should focus on elucidating the functional roles of the identified genes and their implications in DLBCL biology.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
This study reveals two distinct DLBCL subtypes based on PCD-related gene expression, with the C2 subtype identified as high-risk, characterized by enhanced DNA repair and cell cycle pathways.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
The identification of five key biomarkers (CTSB, DPYD, SCARB2, STOM, GBP1) highlights their potential role in refining risk stratification and understanding the molecular heterogeneity of DLBCL.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
These findings provide a foundation for further research into the biological mechanisms underlying DLBCL progression and may contribute to improved prognostic accuracy in future studies.
PMC12003219
Predictive biomarkers and molecular subtypes in DLBCL: insights from PCD gene expression and machine learning
Further investigation is needed to elucidate the functional roles of these biomarkers and their implications for DLBCL biology.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Diffuse large B cell lymphoma (DLBCL) is the most diagnosed, aggressive non-Hodgkin lymphoma, a type of blood cancer.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
In this study, we developed new DLBCL cell-derived xenograft mouse models.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
We found that our models show consistent tumor burden with unformal disease progression and organ-specific infiltration.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Diffuse large B cell lymphoma (DLBCL) is the most diagnosed, aggressive non-Hodgkin lymphoma, with ~40% of patients experiencing refractory or relapsed disease.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Given the low response rates to current therapy, alternative treatment strategies are necessary to improve patient outcomes.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Here, we sought to develop an easily accessible new xenograft mouse model that better recapitulates the human disease for preclinical studies.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
We generated two Luciferase (Luc)-EGFP-expressing human DLBCL cell lines representing the different DLBCL cell-of-origin subtypes.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
After intravenous injection of these cells into humanized NSG mice, we monitored the tumor growth and evaluated the organ-specific engraftment/progression period.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Our results showed that human IL6-expressing NSG (NSG-IL6) mice were highly permissive for DLBCL cell growth.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
In NSG-IL6 mice, systemic engraftments of both U2932 activated B cell-like- and VAL germinal B cell-like-DLBCL (engraftment rate; 75% and 82%, respectively) were detected within 2nd-week post-injection.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
In the organ-specific ex vivo evaluation, both U2932-Luc and VAL-Luc cells were initially engrafted and expanded in the spleen, liver, and lung and subsequently in the skeleton, ovary, and brain.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Consistent with the dual BCL2/MYC translocation association with poor patient outcomes, VAL cells showed heightened proliferation in human IL6-conditioned media and caused rapid tumor expansion and early death in the engrafted mice.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
We concluded that the U2932 and VAL cell-derived human IL6-expressing mouse models reproduced the clinical features of an aggressive DLBCL with a highly consistent pattern of tumor development.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Based on these findings, NSG mice expressing human IL6 have the potential to serve as a new tool to develop DLBCL xenograft models to overcome the limitations of standard subcutaneous DLBCL xenografts.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), constituting 25% to 30% of cases, with approximately 150,000 patients diagnosed annually worldwide .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
DLBCL is a genetically complex hematological malignancy with two major subtypes, the activated B cell-like (ABC) and the germinal center B cell-like (GCB), that correlate with patient prognosis .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Although much progress has been made in treating this disease in that 60% of DLBCL patients will achieve long-term remission with contemporary immuno-chemotherapy , the remaining 40% experience primary refractory disease or relapse .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Several spontaneous and induced B cell lymphoma animal models have been developed using transgenic mice or transplanting with various types of tumor cells to understand mechanisms underlying DLBCL progression .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
These transgenic or transplant xenograft models are limited, as they often fail to recapitulate the heterogeneous subclassifications of this complex disease.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
While transgenic immunocompetent mice allow for spontaneous tumor formation, these models rely on inducing the expression of specific oncogenes that drive a select group of DLBCL.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The transplant xenograft model offers several advantages, such as reproducing late-stage disease and shortening the time of disease development.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Despite these benefits, the current xenograft models are also limited by variable reproducibility and an inability to assess interactions with tumor micro-environments.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Recent studies found that interleukin-6 (IL6) is an important growth factor for normal and malignant B cell engraftment and growth .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The IL6 protein sequence has a 42% similarity between mice and humans.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
While human IL6 works in both human and mouse cell assays, mouse IL6 does not elicit a response in human cells .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The human IL6 presence in the mouse facilitates the engraftment of malignant cells, although no engraftment rate was reported .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Hashwah et al. reported that genetically humanized mouse strains, the MISTRG and MISTRG6, supported better growth of DLBCL cell lines and primary DLBCL cells with inconsistent organ-infiltration patterns via orthotopic injection .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The MISTRG mouse strain expresses human SIRPα, M-CSF, IL-3, GM-CSF, and Thrombopoietin on the immune-deficient mouse (Rag2/IL2Rγ background) under the control of mouse regulatory elements that provide increased support for the development and function of human monocytes, macrophages, and NK cells .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The MISTRG6 mouse is a modified MISTRG with an additional knock-in human IL6 allele and has previously been shown to improve multiple myeloma engraftments and growth .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Here, we employed two different subtypes of DLBCL cells, U2932 (ABC) and VAL (GCB), and intravenously injected them into three strains of immunodeficient mice, NOD-scid-IL2rgnull (NSG) mice expressing human IL6 (NSG-IL6), IL3/CSF2/KITLG (NSG-SGM3), or NSG mice expressing all four human cytokines (NSG-IL6/SGM3), to establish a pipeline for the rapid and reliable generation of in vivo DLBCL models.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
We evaluated these cell-derived xenograft models for early detection, the disease progression pattern, and the organ-specific engraftment and growth.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
All mouse strains were housed and bred at the University of Arkansas for Medical Sciences (UAMS) Animal Facility.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
All animal-handling procedures were reviewed and approved by the UAMS IACUC (AUP #3987 and IPROTO202200000477) and were conducted as per the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Mice were kept on a 12 h light/12 h dark cycle.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Room temperature was maintained at 24–26 °C.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Food pellets and water were sterilized and provided as much as necessary or desired.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
NOD.Cg-Prkdc Il2rg Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ (NSG-SGM3) Mice (JAX stock #013062) and NOD.Cg-Prkdc Il2rg/SzJ (NSG) Mice (JAX stock# 005557) were procured from Jackson Laboratory.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The human IL6-expressing NSG (IL6) strain was generated in Dr. Shultz’s lab by microinjection of a transgenic construct containing the human interleukin-6, IL6, from the 161 Kb BAC clone RP11-469J8.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
This was microinjected into the pronuclei of fertilized NOD.CB17-Prkdc/J eggs.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Founder line 1 was established and mated to NOD.Cg-Prkdc Il2rg/J (Stock No. 005557) mice, and progeny were interbred to produce the NSG-IL6 strain.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The NSG-IL6/SGM3 mice were created by intercrossing the NSG-SGM3 and NSG-IL6 strains and using the F1 progeny that were hemizygous for the four human transgenes.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
We confirmed the genotype by PCR using the following primer sets (IL6, 5′ AGG GAG AGC CAG AAC ACA GA 3′ and 5′ TGC AGC TTA GGT CGT CAT TG 3′; CSF2, 5′ ACC TGC CTA CAG ACC CG 3′ and 5′ AGT GCT GCT TGT AGT GGC 3′; IL3, 5′ AAT CTC CTG CCA TGT CTG C 3′ and 5′ CCA GTC ACC GTC CTT GAT ATG 3′; KITLG, 5′ CAA GGA CTT TGT AGT GGC ATC TG 3′ and 5′ CAA CAG GGG GTA ACA TAA ATG G 3′).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The U2932 and VAL DLBCL cell lines were maintained in RPMI 1640 medium supplemented with 15% fetal bovine serum (FBS), 1× penicillin/streptomycin, and 1× Glutmax (Gibco, Life Technologies, Carlsbad, CA, USA) at 37 °C in an atmosphere of 5% CO2.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
U2932 and VAL cells were cultured at a range of 0.5 to 2 × 10 cells/mL. Cell lines purchased from DSMZ (U2932, ACC-633, RRID:CVCL_1896) or previously obtained from Dr. Rimsza, Mayo Clinic in Arizona, Scottsdale (VAL, RRID:CVCL_1819), and tested for mycoplasma every 6 months with the MycoAlert Mycoplasma Detection Assay (Promega, Madison, WI, USA) and authenticated by the University of Arizona Genetics Core (Tucson, AZ, USA) using the PowerPlex 16 System (Promega, Tokyo, Japan) every 10–12 months (Supplementary Table S1).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Before injection into mice, cells were washed with PBS three times and counted by Cellometer Mini (Nexcelom, Lawrence, MA, USA) using the trypan blue exclusion method and transfected with a Luciferase lentiviral expression system.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
To express Luciferase (Luc) in DLBCL cell lines, U2932 and VAL cells (1 × 10 cells at >90% viability) were transduced with the lentiviral vectors encoding RedFLuc-T2A-EGFP or CBG-T2A-GFP carrying the firefly or beetle green Luc gene using TransDux MAX Lentivirus Transduction Enhancer (System Biosciences, Palo Alto, CA, USA) according to the manufacturer’s protocol.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The GFP-positive cells were sorted after 72 h post-transduction by fluorescence-activated cell sorting (FACS) using a Becton Dickinson (BD) FACS Aria III-Cell Sorter (BD, San Jose, CA, USA).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
U2932-Luc and VAL-Luc cells (0.5 × 10 cells at >90% viability) in 100 µL PBS were injected via the tail vein into NSG, NSG-IL6, NSG-SGM3, or NSG-IL6/SGM3 male and female mice at 8–12 weeks of age.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
An equal number of mice per sex was injected for each mouse strain.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
In vivo bioluminescence imaging (BLI) was conducted on a cryogenically cooled IVIS Imaging System 200 Series (Perkin Elmer, Waltham, MA, USA) using living image acquisition.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Prior to BLI imaging, mice were anesthetized using isoflurane and imaged after 10 min of D-Luciferin (1.5 mg/mouse, Perkin Elmer, Waltham, MA, USA) via intraperitoneal injection.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
All the images were acquired by auto-exposure in the chamber under dim illumination, followed by acquisition and overlay of the pseudo color image representing the spatial distribution of photon counts produced by active Luc within the animal.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Acquired images were analyzed using Living Image Software version 4.7.4 (Perkin Elmer, Shelton, CT, USA), region of interest (ROI) was generated to cover the whole body, and the total flux (p/s) was obtained.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Although the second-week bioluminescence imaging confirmed DLBCL cell engraftment, the mice were continuously imaged once a week.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The mice with no detectable signal by the fourth week post-injection were scored as ‘ungrafted’.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
All other mice were monitored for survival; the median survival of the mice strains was estimated by plotting Kaplan–Meier curves, and the Log-rank test was used to evaluate significant differences between control (PBS) and DLBCL cell-injected mice.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
To evaluate the organ-specific engraftment/progression, we confirmed engraftment in the targeted organs by bioluminescence imaging starting in the second-week post-injection.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
From week 2 up to week 6, 1~4 U2932-Luc- or VAL-Luc- or PBS-injected NSG-IL6 mice were euthanized each week.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
At 10 min after the Luciferin injection, the mice were euthanized, then the intestines, kidney, heart, stomach, spleen, liver, lungs, ovaries, brain, and spine were excised and underwent ex vivo IVIS imaging.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Acquired images were analyzed using Living Image Software version 4.7.4, and region of interest (ROI) was generated to cover the organ area.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
At weeks 2, 3, and 4 post-injection, representative areas of the spleen, liver, and lung of each mouse from the ex vivo imaging were fixed in 10% buffered formalin and embedded in paraffin using a Leica tissue processor.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Sections were cut at 3 μm from the paraffin blocks and mounted onto Superfrost Ultra Plus slides for immunohistochemical staining for human CD20 and counterstained with hematoxylin.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Tissues were deparaffinized with xylene and hydrated in a graded ethanol series to distilled water.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The antigen retrieval step was performed by microwave treatment (5 min) in Tris–EDTA buffer (pH 9.0).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Peroxidase Block Solution and Protein Block Solution were used sequentially to block endogenous peroxidase and to prevent unspecific labeling, respectively.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Tissue sections were incubated 30 min at room temperature with a polyclonal rabbit anti-human CD20 (PIPA532313, Fisher Scientific, Waltham, MA, USA) at a 1:200 dilution.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
CD20 staining was visualized with diaminobenzidine (DAB) and hydrogen peroxide as substrate.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Nuclear background staining was performed with Gill’s hematoxylin for 30 s. Brightfield images of the CD20 stained tissues were taken on a Zeiss AXIO Imager M2 microscope (Zeiss, Nashville, TN, USA) at 200× magnification.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
U2932 and VAL cells were treated in vitro with human IL6 (78148, StemCell Technology, Vancouver, BC, Canada) at 50 ng/mL for 30 min and 60 min.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Cells were harvested, washed with cold PBS, and lysed on ice with RIPA buffer (Boston BioProducts, Milford, MA, USA) and 1× HALT protease/phosphatase inhibitor (ThermoFisher, Waltham, MA, USA) for 30 min.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Lysates were centrifuged at 14,000 rpm for 10 min at 4 °C.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Protein concentrations were quantified using BCA assay (Pierce, ID, USA).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
For each lysate, 100 μg total protein was separated by SDS-PAGE (4–20% Mini-PROTEAN Precast Protein Gels, BIO-RAD) and transferred onto PVDF membranes.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Membranes were probed with antibodies against TBP (ab818, Abcam; 1:2500), STAT3 (79D7, Cell Signaling Technology, Danvers, MA, USA; 1:2000), and p-STAT3 (Tyr705, Cell Signaling Technology; 1:1000).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Secondary antibodies used were goat anti-rabbit Dylight 800 (PISA535571, Thermofisher) and goat anti-mouse Dylight 650, (PISA510174, Thermofisher).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Blots were imaged using the Biorad ChemiDoc MP (BIO-RAD, Hercules, CA, USA), and images were analyzed using Image Lab software v6.1 (BIO-RAD).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
U2932 and VAL cells were plated in 6-well plates at a cell density of 2.5 × 10/mL and equilibrated overnight.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Cells were treated with human IL6 at 50 ng/mL for 2 to 48 h. Viable cells were counted at each time point using trypan blue exclusion on a DeNovix CellDrop BF (DeNovix, Wilmington, DE, USA).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Untreated U2932 and VAL cells were subjected to real-time quantitative PCR (qPCR) analysis to measure mRNA abundance of IL6 receptor subunit α (CD126; Taqman, Hs01075664_m1) and gp130 (Taqman, Hs00174360_m1).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Total RNA was isolated with a Roche High Pure RNA isolation kit (San Francisco, CA, USA), and reverse transcription was performed using the BioRad iScript kit according to the manufacturer’s protocols.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
qPCR was conducted with the BioRad Probe Supermix and TaqMan Probes using the BioRad CFX1000 Touch thermal cycler.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The Ct values were normalized to TATA-binding protein (TBP; Taqman, Hs00427620_m1) and compared to the untreated controls to obtain ∆Ct values.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
For statistical analyses and plots, Student’s t-test, log-rank test, or one-way ANOVA were performed using Prism 7 or 9 (GraphPad Software Inc., San Diego, CA, USA) and Sigma Plot v13.0 (Systat Software Inc., San Jose, CA, USA).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Since DLBCL is a genetically heterogeneous disease with at least two major molecular subtypes, we selected the well-established and characterized U2932 and VAL cell lines as representative of aggressive ABC- and GCB-DLBCL, respectively, to establish our in vivo model .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
U2932 cells harbor extensive BCL2 amplification and mutated CD79B, while VAL cells are positive for BCL2, BCL6, and MYC translocations and CREBBP mutations, all of which are associated with poor patient outcomes .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
To effectively monitor the engraftment and expansion of DLBCL in mice, we transduced the Luc-EGFP gene into DLBCL cells.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The percentages of GFP-positive cells, 47.5% (U2932) and 28.7% (VAL), were exhibited at 72 h post-transduction.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
A successful engraftment of DLBCL in NOD/scid mice was previously showing that subcutaneous passage enhanced the engraftment and metastatic capacity of various DLBCL cell lines .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
Furthermore, successful engraftments of DLBCL cell lines and primary cells were reported in the humanized strains, MISTRG and MISTRG6, that demonstrated the importance of human IL6 in the in vivo engraftment of a subset of DLBCL and the spleen infiltrations of U2932 cells occurred only at MISTRG engrafted with cord blood human hematopoietic stem cells or MISTRG6 .
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
The MISTRG and MISTRG6 strains were not commercially available.
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
We chose the commercially available NSG-SGM3 strain, a previously reported human hematopoietic cell engraftable strain , the recently developed NSG-human IL6 strain, and the F1 strain (NSG-IL6/SGM3).
PMC11394112
Development of New Diffuse Large B Cell Lymphoma Mouse Models
A total of 0.5 × 10 GFP-positive U2932 or VAL cells (>90% viability) were injected into NSG, NSG-IL6, NSG-SGM3, or NSG-IL6/SGM3 mice via the tail vein.