Gilteritinib-based combination therapy in adult relapsed/refractory FLT3-mutated acute myeloid leukaemia.

Gilteritinib, a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib-based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3-mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3-mutated AML, and it may be considered an effective therapy bridge to transplantation.

Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

The value of a new prognostic model developed by lymphocyte-monocyte ratio and platelet-monocyte ratio in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma(PTCL) is a group of lymphoproliferative tumors originated from post-thymic T cells or mature natural killer (NK) cells. It shows highly aggressive clinical behaviour, resistance to conventional chemotherapy, and a poor prognosis. Although a few prognostic models of PTCL have been established in retrospective studies, some high-risk patients still can not be screened out. Therefor we retrospectively studied 347 newly diagnosed PTCL patients and assessed the prognostic role of lymphocyte-monocyte ratio (LMR) and platelet-monocyte ratio (PMR) in the complete response (CR) and survival of PTCL patients. Patients with LMR ≤ 1.68 and PMR ≤ 300 achieved a lower CR rate and a poor survival. In multivariate analysis, LMR ≤ 1.68 (HR = 1.751, 95% CI 1.158-2.647, p < 0.05) and PMR ≤ 300 (HR = 1.762, 95% CI 1.201-2.586, p < 0.05) were independently associated with short survival. On this basis, a new prognostic model of PTCL was established to screen out high-risk patients. In our "Peripheral Blood Score (PBS)" model, three groups were identified at low risk (178 patients, 51.3%, score 0), intermediate risk (85 patients, 24.5%, score 1), and high risk (84 patients, 24.2%, score 2), having a 1-year OS of 86%, 55.3% and 22.6% (p < 0.05), and a 3-year OS of 43.4%, 20% and 13.1% (p < 0.05), respectively. Optimal strategies for identifying high-risk patients with PTCL are urgently needed. Our new PBS model is simple, inexpensive and widely available to screen out the high risk patients.

Association of interleukin-18 gene polymorphism and its protein expression with the lower extremity deep venous thrombosis in the chinese han population: A case-control study.

OBJECTIVE: We aim to explain the correlation among IL-18 gene polymorphism, its protein expression and LEDVT in the Chinese Han population. METHODS: A total of 138 LEDVT patients and 150 healthy people volunteered as LEDVT and control groups. All the data, including the gender, age, BMI, levels of TG, LDL/HDL, TC, GLU, APTT, BUN, Cr, ALT, AST, ApoA1, ApoB, and Fg was detected. IL-18 level, IL-18 -137G/C and -607C/A polymorphism, and risk factors of LEDVT were detected using ELISA, PCR-RFLP and multivariate logistic regression analysis, respectively. RESULTS: Increased BMI, GLU, Fg, BUN, ApoB and IL-18 and decreased APTT were found in the LEDVT group. The GC + CC genotype and C allele in -137G/C polymorphism was elevated in the control group when compared to that in the LEDVT group. The IL-18 level was elevated in the case group when compared to the control group with respect to the same genotype in -607C/A and -137G/C polymorphisms, and in the LEDVT group, IL-18 level was higher in the GG genotype than that in the GC + CC genotype of -137G/C polymorphism. BUN, GG genotype and IL-18 level were independent risk factors, but APTT was a protective factor of LEDVT. CONCLUSION: On the basis of our results, we concluded that the GG genotype of -137G/C polymorphism and IL-18 level are independent risk factors of LEDVT, and IL-18 gene polymorphism affects the level of IL-18 in LEDVT patients.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma.

Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. Methods uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. Results uPAR level in bone marrow fluid of MM patients (1.52±0.32 µg/ml) was found to be higher than that in the control group (0.98±0.15 µg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. Conclusion Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

Prognostic and clinicopathological significance of the Controlling Nutritional Status (CONUT) score in patients with lymphoma: a meta-analysis.

OBJECTIVES: The role of the Controlling Nutritional Status (CONUT) scores in predicting the prognosis of lymphoma cases has been extensively explored, with no consistent results. The present meta-analysis focused on accurately evaluating whether CONUT could be used to predict the prognosis of lymphoma cases and its clinicopathological value. DESIGN: The present meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The prognostic significance of CONUT to overall survival (OS) and progression-free survival (PFS) in lymphoma was estimated by calculating pooled HRs with 95% CIs. The relationship between CONUT and clinicopathological characteristics was measured based on pooled ORs with 95% CIs. DATA SOURCES: PubMed, Web of Science, Embase and Cochrane Library databases were comprehensively searched from inception through 24 March 2023. STATISTICAL METHODS: Either a random-effects model or a fixed-effects model was selected depending on the level of heterogeneity among the included studies. RESULTS: This meta-analysis enrolled seven articles, containing 2060 patients with lymphoma. According to the pooled analysis, a higher CONUT score significantly predicted poor OS (HR=1.94, 95% CI 1.46 to 2.57, p<0.001) as well as poorer PFS (HR=1.51, 95% CI 1.04 to 2.20, p=0.031). Furthermore, according to the combined analysis, a higher CONUT score was significantly associated with Ann Arbor stages III-IV (OR=3.75, 95% CI 2.96 to 4.75, p<0.001), an Eastern Cooperative Oncology Group performance status of 2-4 (OR=5.14, 95% CI 3.97 to 6.65, p<0.001), high-intermediate/high National Comprehensive Cancer Network International Prognostic Index (OR=8.05, 95% CI 5.11 to 12.66, p<0.001), B symptoms (OR=4.97, 95% CI 2.89 to 8.52, p<0.001), extranodal disease (OR=3.25, 95% CI 2.24 to 4.70, p<0.001), bone marrow involvement (OR=4.86, 95% CI 3.25 to 7.27, p<0.001) and elevated lactate dehydrogenase levels (OR=3.21, 95% CI 2.37 to 4.34, p<0.001). CONCLUSIONS: According to our results, higher CONUT scores were significantly associated with poor OS and PFS in lymphoma.

EBV-positive Nodal T-Cell and NK-Cell Lymphoma: A Study of 26 Cases Including a Subset With Strong CD30 Expression Mimicking Anaplastic Large Cell Lymphoma.

Epstein-Barr virus (EBV)-positive nodal T-cell and NK-cell lymphoma is a rare neoplasm of cytotoxic T-cell or NK-cell lineage. Here, we report 26 cases affecting 14 men and 12 women with a median age of 52 years. All patients presented with disease involving multiple lymph nodes, and 20 of 22 (91%) fully staged patients had advanced Ann Arbor stage disease. Spleen, liver, and bone marrow were involved in 70%, 50%, and 52% of cases, respectively. These patients had a dismal prognosis with a median survival of 30 days. Histologically, lymph nodes were replaced by lymphoma in a diffuse pattern. Lymphoma cells were variable in size and large cell morphology was seen in 62% of cases. The neoplastic cells were CD4-/CD8- in 14 (54%) cases and CD4-/CD8+ in 12 (46%) cases. CD56 was positive in 14 (54%) cases. CD30 was positive in 20 (77%) cases; a strong and diffuse pattern was observed in 14 (54%) cases, mimicking, in part, anaplastic large cell lymphoma (ALCL). CD30 expression was associated with younger age and large cell morphology. In summary, EBV+ nodal T-cell and NK-cell lymphoma is an aggressive disease with a poor prognosis. These neoplasms are heterogeneous at the morphologic and immunophenotypic levels. Diffuse and strong expression of CD30 could potentially lead to a misdiagnosis of ALCL if EBV evaluation is not performed. Distinguishing between EBV+ nodal T-cell and NK-cell lymphoma from ALCL is important because treatment strategy and prognosis differ. CD30 expression offers a potential therapeutic target for patients with this aggressive disease.

Prognostic and clinicopathological impacts of systemic immune-inflammation index on patients with diffuse large B-cell lymphoma: a meta-analysis.

Background: The systemic immune-inflammation index (SII) represents the immunoinflammatory score and can be considered as a prognostic marker; however, its relevance to the prognosis in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. Objectives: The present meta-analysis was conducted to comprehensively evaluate the relationship between the SII and prognosis in patients with DLBCL. Design: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources and methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were comprehensively searched from inception to 16 March 2023. We calculated combined hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the prognostic significance of the SII for overall survival (OS) and progression-free survival (PFS) in DLBCL. In addition, this study determined odds ratios (ORs) and their 95% CIs to evaluate the correlation of SII with the clinicopathological features of DLBCL. Results: Five articles including 592 cases were enrolled in the current meta-analysis. According to our combined findings, the higher SII significantly predicted worse OS (HR = 3.87, 95% CI: 2.48-6.04, p < 0.001) together with inferior PFS (HR = 2.38, 95% CI: 1.12-5.08, p = 0.024) in DLBCL. Furthermore, a high SII was significantly correlated with B symptoms (OR = 2.52, 95% CI: 1.66-3.81, p < 0.001), III-IV Ann Arbor stage (OR = 2.86, 95% CI: 1.84-4.45, p < 0.001), high-intermediate/high National Comprehensive Cancer Network International Prognostic Index (OR = 2.25, 95% CI: 1.52-3.31, p < 0.001), increased neutrophil-to-lymphocyte ratio (OR = 33.76, 95% CI: 17.18-66.35, p < 0.001), and increased platelet-to-lymphocyte ratio (OR = 44.65, 95% CI: 5.80-343.59, p < 0.001). Nonetheless, the SII was not significantly related to sex, age, lactic dehydrogenase level, Eastern Cooperative Oncology Group performance status, or histology. Conclusion: According to this meta-analysis, the higher SII dramatically predicted inferior OS and PFS of DLBCL. Furthermore, an increased SII significantly correlated with some clinicopathological features representing the disease progression of DLBCL. Trial registration: The protocol was registered in INPLASY under the number INPLASY202380106.

The role of serum-free light chain ratios in the prediction of poor prognosis in multiple myeloma patients: a systematic review and meta-analysis.

BACKGROUND: The association between the serum free light chain (sFLC) ratio and the prognosis of multiple myeloma (MM) patients is controversial. AIM: The purpose of this study is to explore the relationship between the sFLC ratio and the prognosis of MM patients through meta-analysis. METHODS: Online public databases were searched to find relevant studies. The retrieval time is limited from the establishment of the database to July 2021. The overall survival (OS) and progression-free survival (PFS) rates were compared. The results were described using hazard ratio (HR) and a 95% confidence interval (CI). Qualitative studies were also included. RESULTS: A total of 9 studies involving 2864 participants were included. A pooled analysis based on four studies including newly-diagnosed MM patients, demonstrated that an abnormal sFLC ratio was associated with poor outcomes of OS (HR = 1.82, 95% CI: 1.15-2.90) and PFS (HR = 1.87, 95% CI: 1.20-2.90). Three qualitative studies showed that an abnormal sFLC ratio was related with poor outcomes of OS (studies all included newly diagnosed MM patients) and PFS (two studies included newly-diagnosed MM patients and one study included non-newly-diagnosed MM patients). Two studies stated that the sFLC ratio is not associated with OS (both studies included non-newly-diagnosed MM patients) and one study reported that the sFLC ratio is not associated with PFS (study included non-newly-diagnosed MM patients). CONCLUSION: sFLC ratio could be used to predict adverse outcomes in newly-diagnosed MM patients, but is not suitable for non-newly-diagnosed MM patients.

A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With SF3B1 Mutation.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

Risk factors for anemia in patients with chronic kidney disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Anemia in patients with chronic kidney disease (CKD) presents significant impacts on patients, the health-care system, and financial resources. Therefore, this study aimed to identify the risk factors of anemia among CKD patients. METHODS: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. Studies were identified through systematic searches in September 2021 with no restrictions on date and time, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. The search was conducted using the following terms and phrases: "anemia", "risk factors", "associated factors", "chronic kidney injury", "chronic kidney disease", and "chronic renal insufficiency". The quality of each included study was assessed according to the Newcastle-Ottawa scale. Meta-analysis was performed using STATATM version 14 statistical software for WindowsTM. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: This meta-analysis may help policymakers and program managers design evidence-based interventions on preventing the occurrence of anemia with CKD patient populations.

Interleukin-6 gene-174 G/C promoter polymorphism is not associated with multiple myeloma susceptibility: evidence from meta-analysis: A systematic review and meta-analysis.

PURPOSE: Presently, whether interleukin-6 (IL-6) gene-174 G/C promoter polymorphism is correlated to the susceptibility of multiple myeloma (MM) remains controversial. For this reason, the method of meta-analysis was applied to exploring the association between IL-6 gene-174 G/C promoter polymorphism and MM. METHOD: Two independent researchers systematically searched PubMed, EMBASE, Google academic, Cochrane Library and Chinese literature databases to screen case-control studies on IL-6 gene-174 G/C promoter polymorphism and MM susceptibility. The retrieval period was limited from the formation of the database to January 2020, and data analysis was conducted by employing Stata 11.0 software. RESULT: Seven articles were ultimately included in the present study, including 594 MM patients and 681 controls. Integration analysis exhibited that compared with GC or CC genotype, GG genotype did not increase MM susceptibility (OR = 0.95, 95% CI 0.75-1.22; OR = 0.79, 95% CI 0.52-1.19, respectively). Further, in comparison with CC genotype, GC genotype also presented no effect on increasing MM susceptibility (OR = 0.79, 95% CI 0.53-1.16), while compared with GC+CC genotype, GG genotype had no significant relationship with MM susceptibility (OR = 0.94, 95% CI 0.75-1.19). In subsequent analysis, an observation was made that allele G or C was not related to MM susceptibility (OR = 0.92, 95% CI 0.76-1.12). Funnel chart and Begg test did not reveal publication bias in the included articles. CONCLUSION: The results of the present study advocate that there is no testimony to support the relationship between IL-6 gene-174 G/C promoter polymorphism and MM susceptibility.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Increased Serum Level of Interleukin-10 Predicts Poor Survival and Early Recurrence in Patients With Peripheral T-Cell Lymphomas.

Peripheral T cell lymphoma (PTCL) is an alloplasm group of aggressive and lymphoproliferative tumors with heterogeneous morphological changes of mature T cell immunophenotype. It has multiple subtypes and most of them have poor prognosis. Interleukin 10 (IL-10) is one kind of multi-cell-derived and multifunctional cytokine. It regulates the growth and differentiation of cells, participates in inflammation and immune response, plays an important role in tumor and infection, and is closely related to blood system diseases. Therefore, we implemented a retrospective study of 205 patients who were newly diagnosed with PTCL to explore the relationship between IL-10 and prognosis and early recurrence. We found patients with IL-10 ≥3.6 pg/ml achieved a lower CR rate and higher 1-year recurrence rate than patients with IL-10 <3.6 pg/ml (14.4 vs. 51.9%; 17.6 vs. 49.5%). On multivariate analysis, moreover, elevated IL-10 is an extremely important prognostic factor in PTCL, which can lead to worsening of overall survival (OS), low complete response (CR) rate and higher early relapse rate. Therefore, measurement of IL-10 levels in peripheral blood at the initial stage are useful for predicting the prognosis and helping us to make different treatment plans for individual patients. In the near future, IL-10 inhibitors or antagonists may become a new method of immunotargeting therapy for patients with PTCL.

Bortezomib-Based Regimens for Newly Diagnosed Multiple Myeloma in China: A Report of 12-Year Real-World Data.

Background: Improve the treatment quality might affect patients' efficacy and survival. Methods: Five hundred thirty multiple myeloma patients treated in four hematological centers in China from February 2006 to August 2018 were enrolled. General characteristics, treatment regimens and cycles, efficacy, survival and adverse events of the patients treated before and after August 2013 (later refer to as the before-2013 and after-2013 group) were analyzed and compared. Results: The results suggested that patients who received optimized treatment regimen and route of administration completed more cycles of treatment in the after-2013 group. Although the overall response rate was similar between the two groups (88.6 vs. 90.5%), patients in the after-2013 group had higher complete remission rate (39.1 vs. 28.6%) and better progression-free survival. Subgroup analysis suggested that patients aged 65 years and older, with non-high-risk D-S, ISS, and R-ISS stages, had a significant benefit in progression-free survival. Conclusion: Therefore, in clinical practice in China, by reducing the economic burden brought by the treatment on patients and optimizing the treatment regimen, more patients can be treated with better regimens in a prolonged duration to achieve better efficacy and survival, especially in elderly and non-high-risk patients.

The molecular mechanisms underlying BCR/ABL degradation in chronic myeloid leukemia cells promoted by Beclin1-mediated autophagy.

Background: The development of drug resistance and the persistence of leukemia stem cells are major obstacles for the use of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML). The induction of autophagic death in tumor cells represents a new route for leukemia treatment. Our previous study showed that infection of CML cells with oncolytic viruses carrying the autophagy gene Beclin1 downregulated BCR/ABL protein expression and significantly increased the killing effect of the oncolytic viruses on CML cells via autophagy activation. However, the specific molecular mechanisms underlying the regulation of BCR/ABL and Beclin1-dependent CML cell killing remain unclear. Methods: A physical interaction between BCR/ABL and Beclin1 was characterized via GST-pulldown, co-IP and dual-luciferase reporter assays. Cell proliferation was examined via CCK-8 and clone formation assays. The expression levels of the related proteins were measured via Western blotting. Autophagosomes were observed under transmission electron microscopy. Lentiviral vectors carrying Atg7/UVRAG shRNA or the Beclin1 gene were used to modulate the expression levels of the indicated genes. Immunofluorescence were performed to examine colocalization of BCR/ABL and p62/SQSTM1. CD34+CD38- cells were isolated from bone marrow samples from CML patients via fluorescence-activated cell sorting. Results: In this study, we observed that Beclin1 directly interacts with BCR/ABL. Beclin1 inhibited the activity of the BCR/ABL promoter to downregulate the level of BCR/ABL protein and to promote the downstream colocalization of p62/SQSTM1 and BCR/ABL to autolysosomes for degradation via activation of the autophagy signaling pathway. In CML cell lines, primary cells and CD34+CD38- leukemia stem cells, Beclin1 overexpression significantly inhibited cell growth and proliferation and induced autophagy. Conclusion: Taken together, our results suggest that autophagy induction via Beclin1 overexpression might offer new approaches for treating TKI-resistant CML and for promoting the clearance of leukemia stem cells, both of which have important clinical implications.

Efficacy of vitamin D plus calcium with/without alendronate on bone metabolism in immunologic thrombocytopenic purpura patients with steroid treatment: Nine-month results of a randomized, double-blinded, controlled trial.

Bone loss is a prominent complication in immunologic thrombocytopenic purpura (ITP) patients with steroid treatment. Anti-osteoporotic medications are applied as a therapeutic strategy to prevent bone deterioration in ITP patients. However, the skeletal protective effect of alendronate (ALN) in ITP patients has been rarely reported. The present study was performed to determine whether ALN reduces bone loss in ITP patients. A total of 40 ITP patients with steroid treatment were randomized into a placebo group [n=20; caltrate D (CalD)] and an ALN (10 mg/day) + CalD group (n=20). The patients received CalD or CalD + ALN treatment for 9 months. The primary outcomes were bone mineral density (BMD) in the lumbar vertebrae (L1-L4), femoral neck and total hip, as well as bone metabolism markers. The results indicated that the BMD of the lumbar vertebrae (L1-L4), femoral neck and total hip was significantly increased after ALN + CalD treatment for at 6 and 9 months compared with the baseline. Compared with CalD treatment alone, CalD combined with ALN significantly elevated the BMD at the three skeletal sites at 9 months. Compared with the baseline levels or CalD treatment alone, ALN together with CalD treatment markedly reduced urinary Ca excretion and the serum levels of the bone resorption markers tartrate resistant acid phosphatase 5b and C-terminal telopeptides of type 1 collagen, at 9 months. In conclusion, treatment with ALN together with CalD significantly elevated the BMD at three skeletal sites, and inhibited urinary Ca excretion and the activity of bone resorption markers in patients with ITP.

IRF-3 gene polymorphisms are associated with the susceptibility to and the survival in chronic lymphocytic leukemia and could also serve as an auxiliary index.

The objective of this article was to investigate the relationship between IRF-3 gene polymorphisms and the susceptibility and prognosis of CLL. Between January 2011 and August 2012, 108 CLL patients and 112 healthy were enrolled in the study. DHPLC and Shesis software were applied in our study. In rs7251, CG genotype may increase the CLL risk. In the rs2304206, the alleles T may increase the CLL risk. The GTC haplotype can decrease the CLL risk in normal people, the GTT haplotype can increase the CLL risk in normal people. After treatment, in the rs7251, the event-free survival (EFS) in patients carrying CC genotype was higher than those carrying CG + GG genotype. In the rs2304206, the EFS in patients carrying CC genotype was higher than those carrying CT + TT genotype. IRF-3 gene polymorphisms were associated with the susceptibility and prognosis of CLL, it can be used as an auxiliary index for clinical detection of CLL.

Prognostic significance of SETBP1 mutations in myelodysplastic syndromes, chronic myelomonocytic leukemia, and chronic neutrophilic leukemia: A meta-analysis.

OBJECTIVES: This meta-analysis investigates the prognostic effect of SET binding protein 1 (SETBP1) mutations in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL). METHODS: Eligible studies from Pubmed, Embase, and Web of Science were searched from database inception through April 2016. Hazard ratios (HRs) and 95% confidence interval (CI) of overall survival (OS) were pooled to calculate the prognostic significance of SETBP1 mutation in patients. RESULTS: A total of 12 studies with 2321 patients were included in this meta-analysis; 4 studies for MDS, 5 studies for CMML, and 3 studies for CNL. Pooled results suggested that MDS and CMML patients with SETBP1 mutations had a significantly poorer prognosis when compared with patients with wild-type SETBP1 (MDS: HR = 1.808, 95% CI (1.218-2.685), P = 0.001; CMML: HR = 2.223, 95% CI (1.493-3.308), P<0.001). SETBP1 mutations in CNL patients however, showed no significant effect on the overall survival (HR = 1.773, 95% CI (0.877-3.582), P = 0.111). The Begg's and Egger's tests did not show significant publication bias in any groups. CONCLUSIONS: Current evidence shows that SETBP1 mutation is associated with a poor prognosis in patients with MDS and CMML, but not in patients with CNL.