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Purpose Hepatosplenic T-cell lymphoma (HSTCL), mostly derived from γδ T cells, is a rare but very aggressive lymphoma with poor outcomes. In this study, we generated the first single cell landscape for this rare disease and characterized the molecular pathogenesis underlying the disease progression. Methods We performed paired single cell RNA-seq and T cell receptor (TCR) sequencing on biopsies from a HSTCL patient pre- and post- chemotherapy treatments. Following by a series of bioinformatics analysis, we investigated the gene expression profile of γδ HSTCS as well as its tumor microenvironment (TME). Results We characterized the unique gene expressing signatures of malignant γδ T cells with a set of marker genes were newly identified in HSTCL (AREG, PLEKHA5, VCAM1 etc.). Although the malignant γδ T cells were expanded from a single TCR clonotype, they evolved into two transcriptionally distinct tumor subtypes during the disease progression. The Tumor_1 subtype was dominant in pre-treatment samples with highly aggressive phenotypes. While the Tumor_2 had relative mild cancer hallmark signatures but expressed genes associated with tumor survival signal and drug resistance (IL32, TOX2, AIF1, AKAP12, CD38 etc.), and eventually became the main tumor subtype post-treatment. We further dissected the tumor microenvironment and discovered the dynamically rewiring cell–cell interaction networks during the treatment. The tumor cells had reduced communications with the microenvironment post-treatment. Conclusions Our study reveals heterogenous and dynamic tumor and microenvironment underlying pathogenesis of HSTCL and may contribute to identify novel targets for diagnosis and treatment of HSTCL in the future.

The Brassicaceae is an important plant family. We built a user-friendly, web-based, comparative, and functional genomic database, The Brassicaceae Genome Resource (TBGR, http://www.tbgr.org.cn), based on 82 released genomes from 27 Brassicaceae species. The TBGR database contains a large number of important functional genes, including 4,096 glucosinolate genes, 6,625 auxin genes, 13,805 flowering genes, 36,632 resistance genes, 1,939 anthocyanin genes, and 1,231 m6A genes. A total of 1,174,049 specific guide sequences for clustered regularly interspaced short palindromic repeats and 5,856,479 transposable elements were detected in Brassicaceae. TBGR also provides information on synteny, duplication, and orthologs for 27 Brassicaceae species. The TBGR database contains 1,183,851 gene annotations obtained using the TrEMBL, Swiss-Prot, Nr, GO, and Pfam databases. The BLAST, Synteny, Primer Design, Seq_fetch, and JBrowse tools are provided to help users perform comparative genomic analyses. All the genome assemblies, gene models, annotations, and bioinformatics results can be easily downloaded from the TBGR database. We plan to improve and continuously update the database with newly assembled genomes and comparative genomic studies. We expect the TBGR database to become a key resource for the study of the Brassicaceae.

Cancer is the world's biggest health problem and cancer-induced mortality happened all over the planet after the heart disease. The present study was to scrutinize the anti-leukemia effect of diosmin against Dalton Ascitic Lymphoma (DAL) induced leukemia in mice. DAL cell was used for induction the solid tumor. Body weight, life spans, tumor volume and mean survival time was estimated. Antioxidant, biochemical and pro-inflammatory cytokines were estimated. Diosmin showed the cell viability effect at dose dependent manner against the both cell lines. DAL induced solid tumor mice showed the decreased body weight, mean survival days, non viable cell count and increased the tumor volume, viable cell count and diosmin significantly (p < 0.001) reverse the effect of DAL. Diosmin significantly (p < 0.001) altered the hematological, differential leukocytes, antioxidant, biochemical, pro-inflammatory cytokines at dose dependently. Collectively, we can say that diosmin might alter the DAL induced abnormality via antioxidant and anti-inflammatory effects.

Cancer is still remain as a global burden with the 18.1 million and 9.6 million new cases and mortlities, respectively estimated globally. Leukemia may arise at all ages varied from the infants to elders. In this exploration, we planned to evaluate the antiproliferative effect of D-pinitol on human leukemia MOLT-4 cells. Anticancer potential of D-pinitol was examined using MTT assay. Reactive oxygen species (ROS) generation was studied by fluorescence microscopic method using DCFH-DA staining. Apoptotic morphological alterations were determined by dual staining (acridine orange and ethidium bromide). Western blot and ELISA methods were employed to study apoptotic protein expression. D-pinitol treatment significantly induced cytotoxicity in human leukemia MOLT-4 cells. We observed that D-pinitol induces the generation of ROS in MOLT-4 cells. Further, we noticed that D-pinitol significantly induced apoptosis in a dosage dependent manner. Moreover, western blot and ELISA based analysis revealed that D-pinitol elevated the Bax, Caspase-3, Caspase-9 and attenuated the Bcl-2 expression in leukemic cancer cell. Our findings suggest that D-pinitol treatment induces the apoptosis in human leukemic cells by generating intracellular ROS and modulating apoptotic protein expression.

Background: A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM. Methods: A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ2 test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively. Results: The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 109/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM. Conclusion: Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.

Background The Phase III TOURMALINE-MM4 Trial demonstrated that the oral proteasome inhibitor, Ixazomib maintenance significantly improved progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing ASCT. However, patient recruitment for clinical trials is highly selective so the extent to which study populations represent real-world patients is unclear. Currently, data validating the use of ixazomib maintenance in clinical practice in Chinese landscape is scarce. Methods we conducted a retrospective, observational study of NDMM patients meeting International Myeloma Working Group (IMWG) criteria, who received ixazomib-based maintenance therapy. Data was collected from 26 medical centers in southern China. Enrollment was stratified by risk stage, transplant status and maintenance regimens. The characteristics, toxicities and survival outcomes were recorded. Results We included 105 NDMM patients who received ixazomib-based maintenance treatment. Mean age at diagnosis was 59.82 ± 9.80 years, with 62.9% male patients. MM International Staging System (ISS), stage 3 was the most common with 49.04% of patients; 62.86% had an Eastern Cooperative Oncology Group performance score ≥2, and 81.9% with concomitant diseases. By the end of over 70 months follow-up since initial diagnosis, median PFS was 69.45 (95%CI: 31.42-107.48) months, and median OS was not achieved yet. We explored potential influencing factors of progression at the post-maintenance evaluation with a crude model using logistic regression. Difference in PFS was not statistically significant by status at pre-maintenance response, transplantation, maintenance therapy regimens (single/two/three-agent) and dexamethasone in maintenance regimens (p >0.05). Eight patients (7.62%) had grade≥3 treatment-emergent adverse events (TEAEs); 5.7% discontinued treatment because of TEAEs. Common any-grade TEAEs included fatigue (18.1%), diarrhea (16.19%), and peripheral neuropathy (11.43%). Conclusion Although there are certain differences in maintenance treatment options for newly diagnosed multiple myeloma patients in real-world practice, the results of our retrospective study support that the ixazomib-based maintenance therapy was effective with acceptable toxicity and single-agent ixazomib maintenance provided enough clinical benefit compared to two or three agents. Keywords: multiple myeloma, ixazomib, maintenance therapy, real-world practice Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The immune system plays a pivotal role in defending against infection and cancer immunosurveillance during the onset and procession of malignant disease. Cancer patients are frequently immunocompromised and subject to refractory infection and relapse of leukemia, due to the cytotoxic agents and immunosuppressive glucocorticoids in the chemotherapy regimens. Bu Shen Hui Yang Fang (BSHY), a traditional Chinese compound, was widely used in China to enhance the immune system of leukemia patients combined with chemotherapy and effectively lowered their risk of infection, with specific mechanism unknown yet. Thus, we investigated the effects of BSHY on the immune system using immunosuppressive mouse models. By analyzing the immune system of immunosuppressed BALB/C mice induced by hydrocortisone, we found an increase of CD4+ and CD8+ lymphocytes in the spleens of mice after BSHY treatment. Furthermore, we found the enhanced immune system in BSHY treated group was due to increased proliferation and decreased apoptosis of lymphocytes. Cytokine array analysis revealed that interleukin 4 (IL-4) was reduced in the plasma of immunosuppressed mice but returned to a normal level after BSHY treatment. Moreover, we found IL-4 was an adverse prognostic factor in acute myeloid leukemia patients and part of them could be elevated by BSHY. Mechanistically, we found BSHY enhances the proliferation of lymphocytes in a Stat6-dependent manner. In summary, our current study demonstrates that BSHY enhances the proliferation of lymphocytes in the immunosuppressed mice via upregulating IL-4 signaling.

Background: Leukemia is known to be a common type of cancer mostly affecting children. The standard therapeutic treatment available for leukemia has many drawbacks with serious side effects. Therefore, plant-based chemotherapeutic agents that show less/no toxic side effects might be an efficient way to treat leukemia. Therefore, in this study, we aimed to explore the potential of β-caryophyllene, obtained from various plants sources, and found that it persuades oxidative stress-associated apoptosis during the repression of inflammation and proliferation in MOLT-4 leukemia cancer cells. Materials and Methods: In this study, MOLT-4 cells were incubated with β-caryophyllene (15 and 20 μM) for 24 h and found that β-caryophyllene increased the level of cytotoxicity and reactive oxygen species (ROS) and decreased the level of antioxidants, mitochondrial membrane potential, and apoptotic reaction in MOLT-4 cells. Cell proliferation and apoptosis are important cellular events, and inhibition of cell proliferation along with the generation of proapoptotic marker has been considered as a novel task for treatment of cancer. Results: According to our results, β-caryophyllene induced apoptosis by downregulating the expression of Bcl-2 family of proteins and upregulating the expression of caspases involved in BAX-associated apoptosis in MOLT-4 cells. It also downregulated the expression of biomarkers involved in proliferation (proliferating cell nuclear antigen and cyclin-D1) and inflammation (tumor necrosis factor-α, interleukin-6, nuclear factor-kappa B, and cyclooxygenase-2). Conclusion: In summary, β-caryophyllene potentially induced apoptosis by generating ROS and by inhibiting inflammation and proliferative genes in MOLT-4 leukemia cells.