ALBERT

Beschreibung: Background: According to the 2016 revised World Health Organization (WHO) Classification of Lymphoid Tumors, high grade B-cell lymphoma (HGBL) has been delimited as a new category with two subgroups: HGBL with rearrangements of MYC and BCL2 and/or BCL6 (so-called "double/triple hit lymphoma), and HGBL-NOS (HGBLs with features intermediate between DLBCL and Burkitt lymphoma). Retrospective data indicated many patients with HGBL diagnosed at an advanced stage and often have extremely poor outcome even if they received intensive chemotherapy. The accurate genetic and pathological mechanism of this high-risk lymphoma remains uncertain. For HGBL, traditional scoring may not be systematic enough and has limited reference value, more accurate prognostic grouping indicators are needed. The aim of this study was to evaluate the clinicopathological significances in newly diagnosed HGBL and DLBCL. Several clinical and hematological indexes in concert with Fluorescence in situ hybridization (FISH) rearrangement and Immunohistochemistry (IHC) expression profiles of biomarkers between HGBL and DLBCL will also be analyzed. Methods: We reviewed 52 patients diagnosed as HGBL or DLBCL in our hospital from 2017 to 2018 retrospectively. The clinical and hematological characteristics of the patients including age, gender, Ann-Arbor stage, B symptoms, serum LDH levels, β2-microglobulin (β2-MG), peripheral EBV-DNA copies, white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and IPI score were collected. FISH detection was done in each patient to identify whether the patient had MYC, BCL2, and BCL6 rearrangement. The expressions of the above three indexes were done by IHC as well. NLR (neutrophil to lymphocyte ratio) was definited as ANC/ALC ratio. Results: A total of 52 newly diagnosed patients were included in this study, including 34 (65.4%) males and 18 (34.6%) females. The median age at diagnosis was 54.1 years old (range, 15-88 years), and 22 (42.3%) of them were more than 60 years old. Six patients were classified into the HGBL category and 2 of them were HGBL-NOS subgroup. Twenty-five patients were MYC, BCL2, or BCL6 rearrangement single-positive. Among them, MYC, BCL2, and BCL6 rearrangement were detected in 13.5%, 7.7%, and 30.8% of 52 patients respectively.MYC (cut-off value 〉40%), BCL2 (cut-off value 〉50%), and BCL6 expression was found in 48.1%, 50%, and 65.4% of 52 patients, respectively. Among all of the patients, 32.7% (17/52) CD5 positive and 73.1% (38/52) MUM1 positive. 30.8% (16/52) of them were at stage Ⅰ/Ⅱ and 69.2% (36/52) of them were at stage Ⅲ/Ⅳ. 53.8% (28/52) of the patients had a high blood LDH level, 26.9% (14/52) showed an elevation of β2-MG level (〉3mg/L) and 38.5% (20/52) presented high IPI score (IPI〉2). The baseline clinical, hematological, and pathological characteristics are described in Table 1, 2. 3. With Pearson's Chi-square Tests analysis, the IPI score was significantly higher in patients older than 60 years old (P

Beschreibung: Introduction: Hematopoietic stem cell transplantation (HSCT) is a potentially curative or consolidative therapy for a large number of hematological diseases. Sexual dysfunction (SD) and abnormal level of the sexual hormone are common in patients after HSCT, which are usually caused by intensive myeloablative conditioning. The change of sexual hormone level and SD resulted in the poor quality of life in this population after transplantation. The current aims of this study were to determine: (i) the incidence rate of SD and the association with androgen post both autologous (auto) and allogeneic (allo) HSCT; (ii) multi-factors analysis between SD and clinical characteristics, primary diease, donor type, cGVHD, etc; (iii) the association of androgen with cGVHD and glucocorticoid (GC) therapy. Methods: From April 2010 to February 2019, a total of 126 (74 males and 52 females) patients with hematological diseases undergoing HSCT were enrolled in our study. The reason for the small sample of patients was that only 126 patients completed our Sexual Function Questionnaire. Controls were 108 healthy, age and gender matched persons came from Medical Examiniation Center of our hospital. Assessment indexes included clinical characteristics, donor type, GVHD incidence, sex hormone levels, and Sexual Functioning Questionnaire (SFQ). The SFQ was implemented by the team members of our research group through a telephone interview, email, paper letter, and WeChat. All of the information and privacy of each patient was strictly conserved. Results: 1. Clinical characteristics of the 126 patients who underwent HSCT were shown in Table 1. The median age of the patients was 38 years old (range 16-66) and the follow up after HSCT was from 6 months to 7 years. The predominant disease spectra were multiple myeloma (MM) and acute leukemia in auto- and allo-HSCT group, respectively. Our results showed a significant difference in gender (P

Beschreibung: Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy in some low-risk patients. However, patients with high-risk factors or diagnosed as some special subtypes often have a poor prognosis although they received intensive combine chemotherapy or bio-target treatment. The exact mechanism of the anti-chemotherapy is unknown and it may be related to multiple oncogene mutations and signal pathways. tRFs is reported stability in almost all types of cells and organisms ranging from humans to bacteria. They are highly conserved, tissue-specific and time-specific tRNA fragments and can be detected in body fluid. Their precise sequence structure located at the end of tRNA or nearby. The length of them has a close relationship with the nucleotide composition at cleavage junctions, indicating that the tRFs are derived from tRNA cleavage in a specific manner. tRFs is a group of abundant non-coding RNAs secondly only to miRNAs. It has been proved that tRFs participate in many biological processes including cell proliferation, viral reverse transcriptases activation, gene expression, RNA procession regulation, DNA damage response modulation and tumor suppression. In this study, we aimed to investigate the potential function of associated tRFs in patients with relapsed & refractory (R/R) DLBCL. Materials and Methods Peripheral blood mononuclear cells (PBMCs) were separated from patients with R/R DLBCL and control groups, respectively. Next-generation sequencing and quantitative real-time reverse transcription-PCR were used to determine the expression profiles of tRFs in the two groups. Two databases of tRFs, tRFs2Cancer and tRFdb were utilized to analyse the similarity and dissimilarity of homologous tRNA fragment. Results Among the sequences with significant difference value, ten tRFs were picked, four (sequence 1- sequence 4) were up-regulated and six (sequence 5- sequence 10) were down-regulated (Figure1). To investigate the content of the differentially expressed tRF in patients group, we performed quantitative PCR to verify three tRFs. The PCR result was consistent with the sequencing analysis. Combined with the results of qRT-PCR and database searching (Figure2,3), we finally chose three sequences (sequence 2, sequence 4 and sequence 10) for further study. With the help of TargetScan, miRanda and other target gene predicting tools, we identified the associated target genes for the three tRFs (sequence 2:497, sequence 10: 9114, sequence 4: 730). The regulatory relationship of sequence 4 is shown in figure 4, the color of each line corresponds to the chromosome which the tRNA comes from. Because sequence 10 has a large number of potential regulatory target genes and it is difficult to obtain satisfying results, we made a functional enrichment analysis for the other tRFs to get their potential regulatory genes. The results showed that the potential target genes of sequence 4 tend to be enriched in multiple ways, including plasma membrane-bounded cell projection morphogenesis, nervous system development, and sensory organ development, etc. The potential target genes of sequence 2 tend to be enriched in FCGR-dependent phagocytosis, Ras signaling pathway, and cellular component regulation(Figure 5). The results of protein interactions analysis showed that the potential regulatory target genes of sequence 4 and sequence 2 can be constructed to gene-protein interaction networks. In this network, several biological processes such as alternative splicing, endosomal transport, and endocytosis might play important roles in tumorigenesis(Figure 6). Conclusion In this study, we analyzed the differently expressed tRFs profiles in patients with R/R DLBCL and the results are consistent with the database data analysis. We also predicted the possible mechanism of the up- or down-regulated tRFs which might be used in clinical although they are unexploited yet. Up or down-regulated tRFs is common in many types of tumors. It is well known that knockdown of the overexpressed tRF may inhibit tumor cell proliferation and the recovery of the downregulated tRFs may reverse the sensitivity to chemotherapy. We hyperthesis that the associated tRFs can be used as fluid-based biomarkers for diagnosis and prognosis assessment. Future investigation on them may help to develop new methods to repair the disordered biological signaling pathways associated with the DLBCL. Disclosures No relevant conflicts of interest to declare.