Identification of FAT4 as a positive prognostic biomarker in DLBCL by comprehensive genomic analysis.

The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

Mutational Spectrum and Prognosis Analysis of Young Patients with Diffuse Large B-Cell Lymphoma Based on Next-Generation Sequencing / 中国实验血液学杂志

OBJECTIVE@#To investigate the mutational spectrum in young patients with diffuse large B-cell lymphoma (DLBCL) based on next generation sequencing (NGS), and to provide a basis for in-depth understanding of the molecular biological characteristics and accurate prognosis of young DLBCL.@*METHODS@#From March 2009 to March 2021, 68 young DLBCL patients with complete initial diagnosis data from the Department of Hematology, The People's Hospital Xinjiang Uygur Autonomous Region were retrospectively analyzed, and their paraffin-embedded tissues were subjected to targeted sequencing analysis by NGS technology (including 475 Target genes), and the differences in gene mutation profiles and signaling pathways between high-risk patients with aaIPI ≥2 and low-intermediate risk patients with aaIPI <2 were compared.@*RESULTS@#A total of 44 high-frequency mutation genes were detected in 68 young DLBCL patients. By comparing the high-frequency mutation genes in aaIPI high-risk group and low-intermediate risk group, it was found that CARD11 mutation in aaIPI high-risk group was significantly higher than that in low-intermediate risk group (P =0.002), while MGA mutation (P =0.037) only appeared in the aaIPI high-risk group, and SPEN mutation (P =0.004) only appeared in the aaIPI low-intermediate risk group. The high-frequency mutation genes and clinical indicators of the aaIPI high-risk group were included in the survival analysis, and the results showed that TP53 (P =0.009, P =0.027), POU2AF1 (P =0.003, P =0.006) and CCND3 (P =0.040, P =0.014) genes mutations were associated with worse PFS and OS, while B2M was associated with better PFS (P =0.014) and OS (P =0.013). Multivariate COX regression analysis showed that the TP53, POU2AF1 and CCND3 were independent risk factors for PFS（P ＝0.021，P =0.005，P =0.020） and OS（P ＝0.042，P =0.010，P =0.013）.@*CONCLUSION@#The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.

Distribution and prognostic value of LymphGen genotyping in patients with diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To investigate the distribution characteristics of LymphGen genotyping in a diffuse large B-cell lymphoma (DLBCL) population and verify its prognostic value. Methods: We collected the clinical data and paraffin-embedded tumor tissue samples of 155 patients with newly diagnosed DLBCL in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. DNA was extracted from tumor tissue and 475 gene mutations were detected by next-generation sequencing technology. We investigated the distribution of LymphGen genotyping in the DLBCL population, patients with different COO genotypes in the Xinjiang region, and their effects on PFS and OS. Results: ①Among 155 patients, 105 patients (67.7%) could be genotyped, including 14 (9.0%) for MCD, 26 (16.8%) for BN2, 10 (6.5%) for N1, 8 (5.2%) for EZB, 27 (17.4%) for A53, and 20 (12.9%) for ST2. ②The distribution of each gene subtype was different in different cell origin (COO) types (P=0.021) . ST2 was dominant in the germinal center type (GCB) group (28.8%) , and A53 and MCD were dominant in the non-GCB group (35.8%, 17.0%) . The BN2 type was the most common in both groups (23.1%, 26.4%) . ③There were statistically significant differences in progression-free survival (PFS) and overall survival (OS) among different gene subtypes (P=0.031 and 0.005, respectively) . N1 and A53 had poor prognosis. The 2-year PFS and OS rates of N1 were both (21.3±18.4) %, and the 3-year PFS and OS rates of A53 were (60.9±11.3) %, (46.8±10.9) %, respectively. ④ The 3-year PFS and OS rates of MCD were the best, but the 5-year PFS and OS rates were worse. ⑤In the ROC curve of LymphGen genotyping for OS prediction, the AUC was 0.66, showing a certain degree of differentiation. Conclusion: LymphGen genotyping in the DLBCL population was different from previous reports and was of great significance for the prognosis of patients with DLBCL.

LINC00665 promotes the viability, migration and invasion of T cell acute lymphoblastic leukemia cells by targeting miR-101 via modulating PI3K/Akt pathway.

T cell acute lymphoblastic leukemia (T-ALL) is a high-risk malignancy. The effects of cancer growth-related Long Intergenic Non-Protein Coding RNA 665 (LINC00665) in T-ALL remained obscure, and therefore further exploration was conducted on that in this study. The expression of LINC00665 in acute myeloid leukemia (LAML) tissues and myeloid tissues was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) 2. The target microRNA (miR) of LINC00665 was predicted by LncBase Predicted v.2 and verified using dual-luciferase reporter assay. After LINC00665 and miR-101 in T-ALL cells were overexpressed or silenced, the viability, migration and invasion of cell were detected using cell counting kit-8 and Transwell assays. The expressions of LINC00665, miR-101, Cyclin D1, Matrix metalloproteinases (MMP)-2, MMP-9, phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), PI3K, p-Akt, Akt were detected by quantitative real-time Polymerase Chain Reaction (qRT-PCR) and western blot. High expression of LINC00665 was presented in LAML tissues, the peripheral blood samples from patients with T-ALL and T-ALL cells. Overexpression of LINC00665 promoted the viability, migration and invasion of T-ALL cells and downregulated miR-101 expression, whereas silencing of LINC00665 did oppositely. MiR-101 could competitively bind to LINC00665, and was low-expressed in T-ALL. MiR-101 mimic inhibited viability, migration and invasion of T-ALL cells, and reversed effects of overexpressed LINC00665, whilst miR-101 inhibitor reversed the effects of LINC00665 silencing. Besides, overexpressed LINC00665 upregulated the expressions of Cyclin D1 MMP-2, and MMP-9 and the ratios of p-PI3K/PI3K and p-Akt/Akt, which were reversed by miR-101 mimic. LINC00665 could enhance the viability, migration and invasion abilities of T-ALL cells by targeting miR-101 via activating PI3K/Akt pathway.

Karyotype analysis and relationship with the curative effect in 80 patients with acute lymphocytic leukemia / 肿瘤研究与临床

Objective To explore the chromosome kauotype characteristics and the relationship with curative effect in the acute lymphoblastic leukemia (ALL).Methods The bone marrow cells were collected using a short-term culture method.The R banding technique of chromosome karyotype analysis was used in 80 cases of ALL patients.Results Normal karyotype were found in 53 cases (66.2 ％),and abnormal karyotype in 27 cases (33.8 ％),including structure of chromosome karyotype in 10 cases (12.5 ％),chromosome numerical abnormality in 2 cases (2.5 ％),abnormal complex karyotype in 15 cases (18.8 ％).According to the classification number of distortion,it was found that ＞ 50 diploid in 2 cases (2.5 ％),47-50 diploid in 5 cases (6.25 ％),false diploid in 18 cases (22.5 ％),normal diploid in 53 cases (66.25 ％),the diploid in 2 cases (2.5 ％),it did not shown any karyotype was triploid or nearly four times.The curative effect of normal karyotype was superior to that of the abnormal karyotype (x2 =19.371,P ＜ 0.01),that of complex karyotype had poorer than that of other karyotype (x2 =9.145,P =0.004),and patients accompaning with the t(9;22)(q34;q11) had poorer than that of other karyotype (x2 =5.785,P =0.021).Conclusions The abnormal chromosome karyotype is random.More common abnormal karyotype is complex karyotype and t(9;22) (q34;q11),which curative effects are poorer.

Clinical observation of bortezomib plus dexamethasone regimen for patients with light-chain multiple myeloma / 肿瘤研究与临床

Objective To comparatively analyze the efficiency and toxicity of BD (bortezomib plus dexamethasone) regimen and VAD (vincristine combined with pirarubicin and dexamethasone) regimen for patients with light-chain multiple myeloma (MM).Methods Retrospective investigation of 16 cases of patients with light-chain MM.7 patients were receiving BD regimen and 9 patients were receiving VAD regimen.Results With a median follow-up of 24 months (2-76 months) in BD group,the total response rate (85.7 ％,6/7) was higher than VAD group (55.6 ％,5/9),with no statistical significance (x2 =1.667,P =0.308).But the CR+nCR rate of the BD group (42.9 ％,3/7) was significantly higher than VAD group (0.0 ％,0/9) (x2 =4.747,P =0.029).5 patients with renal dysfunction in BD group,and that of total response rate (80.0 ％,4/5) was higher than VAD group (57.1％,4/7),but with no statistical significance (x2 =0.686,P =0.576).Main adverse effects in BD group were hematologic toxicity combined with infection (42.8 ％,3/7),peripheral neuropathy (28.6 ％,2/7) and digestive reaction (14.3 ％,1/7).These adverse effects were mild (grade 1-2) and could be relieved by symptomatic treatments.The most common adverse events in VAD group were hematologic toxicity combined with infection (44.4 ％,4/9),digestive reaction (33.3 ％,3/9) and hair loss (22.2 ％,2/9).Conclusion Light chain MM has an aggressive clinical course with poor response to treatment and unfavorable prognosis,but BD regimen has significantly improve the overall reaction rate of light chain type MM.BD has higher CR+nCR rate compared with VAD and can be tolerant in most patients.BD is safe in patients with renal inadequacy.

Clinical and laboratory features of Uyghur patients with chronic lymphocytic leukemia in Xinjiang Uyghur Autonomous Region / 白血病·淋巴瘤

Objective To analyze the clinical and laboratory features of Uyghur patients with chronic lymphocytic leukemia(CLL) in Xinjiang Uyghur Autonomous Region.Methods Retrospective investigation of 39 Uyghur patients with CLL in the People' s Hospital of Xinjiang Uyghur Autonomous Region,and analyzed 30 cases of Han nationality patients with CLL choose over the same period as the contrul group.Results The average age of Uyghur and Han nationality CLL patients were (65.6±10.4) years old and (63.9±7.9) years old while the average age was (64.7±9.0) years old of all cases,and there was no statistical significance (P =0.448).By CLL Rai staging,patients in low-risk (phase 0),medium-risk (phase Ⅰ and Ⅱ) and high-risk (phase Ⅲ and Ⅳ) were 6,24 and 39 cases respectively.Among them,Uyghur patients with advanced stage was more than Han nationality patients (P =0.039).The WBC counts in the initial diagnosis and the number of lymph node regions involved ≥3 were statistically significant (t =2.488,P =0.015,x2 =4.194,P =0.041).With a median follow-up time of 38.0 months (8.0-124.0 months),in which 10 cases died,5 cases was Uyghur and 5 cases was Han nationality,and all of them were the high-risk group of CLL patients.The expected 5-year survival rate and the median survival time were (88.0±2.7) ％ and 100.7 months,respectively and both of them shorter than Han nationality patients with CLL [(94.0±3.0) ％ and 151.1 months],but no statistically significant (x2 =2.198,P =0.138,x2 =0.583,P =0.445).Conclusion There are some differences in two nations in the case of characteristics of clinical laboratory examinations and survivals.