Predicting prostate adenocarcinoma patients' survival and immune signature: a novel risk model based on telomere-related genes.

Alterations in telomeres constitute some of the earliest occurrences in the tumourigenesis of prostate adenocarcinoma (PRAD) and persist throughout the progression of the tumour. While the activity of telomerase and the length of telomeres have been demonstrated to correlate with the prognosis of PRAD, the prognostic potential of telomere-related genes (TRGs) in this disease remains unexplored. Utilising mRNA expression data from the Cancer Genome Atlas (TCGA), we devised a risk model and a nomogram to predict the survival outcomes of patients with PRAD. Subsequently, our investigations extended to the relationship between the risk model and immune cell infiltration, sensitivity to chemotherapeutic drugs, and specific signalling pathways. The risk model we developed is predicated on seven key TRGs, and immunohistochemistry results revealed significant differential expression of three TRGs in tumours and paracancerous tissues. Based on the risk scores, PRAD patients were stratified into high-risk and low-risk cohorts. The Receiver operating characteristics (ROC) and Kaplan-Meier survival analyses corroborated the exceptional predictive performance of our novel risk model. Multivariate Cox regression analysis indicated that the risk score was an independent risk factor associated with Overall Survival (OS) and was significantly associated with T and N stages of PRAD patients. Notably, the high-risk group exhibited a greater response to chemotherapy and immunosuppression compared to the low-risk group, offering potential guidance for treatment strategies for high-risk patients. In conclusion, our new risk model, based on TRGs, serves as a reliable prognostic indicator for PRAD. The model holds significant value in guiding the selection of immunotherapy and chemotherapy in the clinical management of PRAD patients.

[Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome].

OBJECTIVE: To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) transformed from myelodysplastic syndrome (MDS). METHODS: The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed. The demographic data and laboratory parameters, cytogenetic karyotypes, target genes of AML detected by next generation sequence, risk stratification, treatment regimen, therapeutic efficacy and survival outcome were documented. Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy. The effects of clinical parameters, risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis. RESULTS: The median overall survival (OS) of the AML-MRC patients was 4.5 months, the 1-year OS rate was 28.3%, and the complete remission (CR) rate after treatment was 33.3%. The univariate analysis showed that age≥60 years, leukocytosis, severe thrombocytopenia, poor-risk group and only accepted hypomethylating agents(HMAs) or supportive therapy were the risk factors affecting OS. COX multivariate analysis showed that thrombocytopenia ( HR=4.46), HMAs therapy (compared to transplantation, HR=10.47), supportive therapy (compared to transplantation, HR=25.80) and poor-risk group (compared to medium-risk group, HR=13.86) were independent hazard factors for median OS of patients with AML-MRC. The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age≥60 years, thrombocytopenia, time of transformation from MDS to AML (TTA)≥3 months, fibrinogen-albumin ratio index (FARI)≥0.07, CONUT score≥5, poor-risk group and supportive therapy. Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age≥60 years ( HR=11.23), thrombocytopenia ( HR=8.71), FARI≥0.07 ( HR=5.19) and poor-risk group ( HR=14.00). The risk factors affecting CR of AML-MRC patients in univariate analysis were age≥60 years, thrombocytopenia, FARI≥0.1, CONUT score≥5, poor-risk group and supportive therapy, while binary logistic regression analysis showed that age≥60 years( HR=7.35), CONUT score≥5 ( HR=9.60), thrombocytopenia ( HR=12.05) and poor-risk group ( HR=32.5) were independent risk factors affecting CR of the patients. CONCLUSION: The OS of AML-MRC patients is poor, old age(≥60 years old), supportive therapy, HMA therapy, poor-risk, thrombocytopenia, FARI≥0.07 and CONUT score≥5 may be associated with poor prognosis.

Association of ulcerative colitis and acute gastroenteritis with prostate specific antigen: results from National Health and Nutrition Examination Survey from (2009 to 2010) and Mendelian randomization analyses.

Background: An increasing number of studies have demonstrated that gastrointestinal inflammation may increase prostate cancer risk and raise the prostate-specific antigen (PSA) level. However, the association between ulcerative colitis (UC) and acute gastroenteritis (AGE) with PSA remains unclear and complicated. Herein, we evaluated the relationship between UC and AGE with PSA concentration using the National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analyses. Materials and methods: A total of 1,234 participants fit into the study after conducting the screening based on the NHANES survey conducted from 2009 to 2010. UC and AGE were the independent variables, and PSA was the dependent variable. Weighted multiple linear regressions were utilized to estimate the association of UC and AGE with PSA concentration. To detect the causal relationship between UC and AGE with PSA, a two-sample Mendelian randomized analysis was conducted. Results: After controlling for all covariates, PSA (log2 transform) concentrations in the UC group were increased by 0.64 (0.07, 1.21). AGE was not independently associated with PSA levels after adjusting potential confounders. In patients with coronary artery disease, AGE promotes elevated PSA (log2 transform) concentrations (ß = 1.20, 95% CI: 0.21-2.20, p < 0.001). Moreover, an IVW MR analysis indicated that genetically predicted UC was associated with increased PSA, and that AGE was not associated with PSA. Conclusion: This study indicated that a positive causal association exists between UC and the PSA level. However, there is no evidence to support the relationship between AGE and the PSA level.

K2Sr4(PO3)10: A Polyphosphate with Deep-UV Cutoff Edge and Enlarged Birefringence.

A new polyphosphate K2Sr4(PO3)10 is synthesized by a high-temperature solution method. This compound crystallizes in the triclinic space group of P1̅, consisting of the 1D infinite [PO3]∞ chains and K and Sr ions between the chains. Compared with AM2(PO3)5 (A = K, Rb, Cs; M = Ba, Pb), K2Sr4(PO3)10 exhibits a more complex [PO3]∞ chain structure and more diverse metal cationic coordination environment. More importantly, K2Sr4(PO3)10 has both a deep-UV cutoff edge (<200 nm) and a significantly enlarged birefringence. First-principles calculations indicate that the birefringence of K2Sr4(PO3)10 is 0.017 at 1064 nm, about 2 times that of RbBa2(PO3)5 (0.008 at 1064 nm), which reaches a new height among the reported mixed alkali metal and alkaline earth metal phosphate. Theoretical calculations and structural analyses show that the enlarged birefringence of K2Sr4(PO3)10 mainly originates from the [PO3]∞ chains arranged in an inverted zigzag. This discovery introduces a new strategy for devising novel phosphate deep-UV optical crystals with a large birefringence.

[Efficacy Analysis of Bendamustine-Based Combination Regimen in Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma].

OBJECTIVE: To investigate the efficacy and safety of bendamustine combined with gemcitabine, vinorelbine，glucocorticoids (BeGEV)±X regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma. METHODS: A total of 18 relapsed/ refractory non-Hodgkin lymphoma patients at the age of 18 years or older hospitalized in the First People's Hospital of Changzhou from March 2020 to March 2021 were selected. They received two or more cycles of BeGEV±X regimen. X could be anti-CD20 monoclonal antibody, PD-1-blocking antibodies, lenalidomide, BTK inhibitor, Bcl-2 inhibitor and so on according to patients' disease feature. The clinical efficacy and adverse effects were observed. RESULTS: In total, 18 patients completed two or more cycles of BeGEV±X regimen, including 14 with diffuse large B-cell lymphoma, one with low-grade follicular lymphoma, one with follicular lymphoma grade 3b, one with angioimmunoblastic T-cell lymphoma and one with peripheral T-cell lymphoma, not otherwise specified. 11 patients were male. The median age of the patients was 64 years old. 17 patients had modified Ann Arbor stage Ⅲ/Ⅳ disease. 13 patients had high- intermediate risk or high risk IPI score, while 15 patients had high-intermediate high risk or high risk NCCN-IPI score. 14 cases had extranodal sites of disease. And 6 cases had bulky disease. 12 patients experienced refractory disease, while 8 patients had received 3 line or more prior treatment. After two or three cycles of chemotherapy, the complete response rate was 6/18, the partial response rate was 3/18, and the objective response rate was 9/18. From the beginning of salvage chemotherapy to the end of follow-up, the median progression-free survival time was 130 days, and the median overall survival was 152 days. The most common grade 3 to 4 adverse events were hematologic toxicities, infection and febrile neutropenia. CONCLUSION: BeGEV±X is an effective salvage regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma, while adverse events such as hematologic toxicities and infection should be closely monitored.

Sodium butyrate treatment and fecal microbiota transplantation provide relief from ulcerative colitis-induced prostate enlargement.

The ability to regulate the gut environment has resulted in remarkable great breakthroughs in the treatment of several diseases. Several studies have found that the regulation of the gut environment might provide relief from the symptoms of benign prostatic hyperplasia. However, the correlation between the gut microenvironment and the colon and prostate glands is still unknown. We found that ulcerative colitis (UC) induced an increase in prostate volumes that could be reversed by sodium butyrate (NaB) and fecal microbiota transplantation (FMT). The mechanism by which UC induced changes in the prostate gland was examined via RNA-Seq. The results show that the expression level of GPER was significantly lower in the prostate gland of UC mices than in normal mices. The expression of GPER could be increased via treatment with NaB or FMT. We found that prostate tissues exhibited higher butryic acid levels after they were treated with NaB or FMT. In experiments conducted in vitro, NaB or the fecal filtrate (FF) from healthy mice up-regulated of the expression of GPER, inhibited cell growth, and induced apoptosis in BPH-1 cells. These changes could be alleviated by treatment with the G15 or in GPER-silenced cells.

[The Clinical Value of Neutrophil CD64 Index in Hematological Malignancies with Pulmonary Infection].

OBJECTIVE: To investigate the clinical value of neutrophil CD64 index in hematological malignancies with pulmonary infection. METHODS: The cohort study method was used to retrospectively analyze the clinical data of 125 patients with hematological malignancies and pulmonary infections who were treated in The Third Affiliated Hospital of Soochow University. All the patients were divided into four stages according to the diagnosis and treatment process: non-infected stage (T1), the symptoms of infection had appeared before using antibiotics (T2), one week after anti-infective treatment (T3), and after stopping antibiotics (T4). CD64 index, C-reactive protein (CRP), blood cell count, and immune cell level were compared before and after infection (T1 vs T2), the correlation between CD64 index and other indicators were explored, the change trends of the significantly different indicators in the course of the disease were observed, and the diagnostic efficacy of CD64 index and CRP were compared. The surviving patients were followed up for whether reinfection occurred within 30 days after discharge, and the re-examination results of indices before discharge (in stage of T4) between reinfected and non-reinfected patients were compared to find the risk factors of reinfection. RESULTS: Before and after infection, the CD64 index, CRP, CD14+HLA-DR+, CD4+, and lymphocyte counts were significantly different (all P<0.05). There was a negative correlation of CD64 index with CD14+HLA-DR+ (r=-0.395, P<0.001), a negative correlation with CD3+ (r=-0.1.87, P=0.047), and a negative correlation with lymphocyte count (r=-0.230, P=0.006), while a positive correlation with CRP(r=0.313, P<0.001). The area under the curve of CD64 index, CRP, and CD64 index combined with CRP was 0.790 (95%CI: 0.711-0.868), 0.754(95%CI: 0.667-0.841), and 0.835(95%CI: 0.762-0.907), respectively; the sensitivity was 59.6%, 72.7%, and 74.7%, the specificity was 89.2%, 73.0%, and 78.4%, and the cut-off value was 0.488, 0.457, and 0.531, respectively. There were only two re-examination indexes showed significantly different before discharge between reinfected patients and non-reinfected patients: CD14+HLA-DR+ (F=8.524, P=0.004) and CD64 index (F=9.993, P=0.002). The increase of CD64 index was an independent risk factor for reinfection within 30 days after discharge from the hospital (HR=1.790, 95%CI: 1.343-2.386, P<0.001). CONCLUSION: CD64 index has diagnostic value in patients with hematological malignancies and pulmonary infection, and its specificity is higher than that of CRP. The combination of the two indicators can improve the diagnostic sensitivity. CD64 index has a predictive value for reinfection within 30 days after infection treatment.

Bortezomib-resistant multiple myeloma patient-derived xenograft is sensitive to anti-CD47 therapy.

Multiple myeloma (MM) remains an incurable hematologic malignancy due to its frequent drug resistance and relapse. Cluster of Differentiation 47 (CD47) is reported to be highly expressed on MM cells, suggesting that the blockade of CD47 signaling pathway could be a potential therapeutic candidate for MM. In this study, we developed a bortezomib-resistant myeloma patient-derived xenograft (PDX) from an extramedullary pleural effusion myeloma patient sample. Notably, anti-CD47 antibody treatments significantly inhibited tumor growth not only in MM cell line-derived models, including MM.1S and NCI-H929, but also in the bortezomib-resistant MM PDX model. Flow cytometric data showed that anti-CD47 therapy promoted the polarization of tumor-associated macrophages from an M2- to an M1-like phenotype. In addition, anti-CD47 therapy decreased the expression of pro-angiogenic factors, increased the expression of anti-angiogenic factors, and improved tumor vascular function, suggesting that anti-CD47 therapy induces tumor vascular normalization. Taken together, these data show that anti-CD47 antibody therapy reconditions the tumor immune microenvironment and inhibits the tumor growth of bortezomib-resistant myeloma PDX. Our findings suggest that CD47 is a potential new target to treat bortezomib-resistant MM.

Novel myeloma patient-derived xenograft models unveil the potency of anlotinib to overcome bortezomib resistance.

Multiple myeloma (MM) remains a common hematologic malignancy with a 10-year survival rate below 50%, which is largely due to disease relapse and resistance. The lack of a simple and practical approach to establish myeloma patient-derived xenograft (PDX) hampers translational myeloma research. Here, we successfully developed myeloma PDXs by subcutaneous inoculation of primary mononuclear cells from MM patients following series tumor tissue transplantations. Newly established myeloma PDXs retained essential cellular features of MM and recapitulated their original drug sensitivities as seen in the clinic. Notably, anlotinib therapy significantly suppressed the growth of myeloma PDXs even in bortezomib-resistant model. Anlotinib treatments polarized tumor-associated macrophages from an M2- to an M1-like phenotype, decreased tumor vascular function, and accelerated cell apoptosis in myeloma PDXs. Our preclinical work not only unveiled the potency of anlotinib to overcome bortezomib resistance, but also provided a more practical way to establish MM PDX to facilitate myeloma research.

Characterization of a Pyroptosis-Related Signature for Prognosis Prediction and Immune Microenvironment Infiltration in Prostate Cancer.

This study was aimed at constructing a pyroptosis-related signature for prostate cancer (PCa) and elucidating the prognosis and immune landscape and the sensitivity of immune checkpoint blockade (ICB) therapy in signature-define subgroups of PCa. We identified 22 differentially expressed pyroptosis-related genes in PCa from The Cancer Genome Atlas (TCGA) database. The pyroptosis-related genes could divide PCa patients into two clusters with differences in survival. Seven genes were determined to construct a signature that was confirmed by qRT-PCR to be closely associated with the biological characteristics of malignant PCa. The signature could effectively and independently predict the biochemical recurrence (BCR) of PCa, which was validated in the GSE116918 and GSE21034. We found that patients in the high-risk group were more prone to BCR and closely associated with high-grade and advanced-stage disease progression. Outperforming clinical characteristics and nine published articles, our signature demonstrated excellent predictive performance. The patients in the low-risk group were strongly related to the high infiltration of various immune cells including CD8+ T cells and plasma B cells. Furthermore, the high-risk group with higher TMB levels and expression of immune checkpoints was more likely to benefit from immune checkpoint therapy such as PD-1 and CTLA-4 inhibitors. The sensitivity to chemotherapy, endocrine, and targeted therapy showed significant differences in the two risk groups. Our signature was a novel therapeutic strategy to distinguish the prognosis and guide treatment strategies.

Overexpression of miR-17 predicts adverse prognosis and disease recurrence for acute myeloid leukemia.

BACKGROUND: The clinical significance of miR-17 in patients with acute myeloid leukemia (AML) remains unknown. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (qPCR) was performed to detect the miR-17 expression in 115 de novo AML patients, 31 patients at complete remission (CR) time, 8 patients at relapse time and 30 normal controls. RESULTS: MiR-17 was upregulated in de novo AML compared with normal controls. Patients with high expression of miR-17 had less CEBPA double mutation, less favorable ELN-risk and lower CR rate. The level of miR-17 was significantly decreased at CR phase and was returned to primary level even higher when in relapse phase. In addition, Cox regression analysis revealed that miR-17 expression retained independent prognostic significance for overall survival (OS). Moreover, the gene-expression profile analysis of miR-17 in AML obtained from TCGA database was involved in multiple biological functions and signal pathways. Among the differential expressed genes (DEGs), we identified FGL2, PLAUR, SLC2A3, GPR65, CTSS, TLR7, S1PR3, OGFRL1, LILRB1, IL17RA, SIGLEC10, SLAMF7, PLXDC2, HPSE, TCF7 and MYCL as potential direct targets of miR-17 according to in silico analysis. CONCLUSIONS: High expression of miR-17 in de novo AML patients pointed to dismal clinical outcome and disease recurrence, which could serve as novel prognostic biomarker for AML patients.

[The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms].

OBJECTIVE: To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients. METHODS: Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared. RESULTS: There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group. CONCLUSION: The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential.

Background and aim: Silencing the expression of ACACA inhibits cell proliferation and induces apoptosis in prostate cancer LNCaP cells. However, the role of ACACA in other prostate cancer cells is not fully understood. Also, the effect of knocking down ACACA gene on mitochondria remains unclear. This study aimed to discover the specific role of ACACA gene in prostate cancer (PCa) DU145 and PC3 cells as well as its effects on mitochondrial potential. Methods: The expression of ACACA gene was detected in human prostate cancer tissue microarrays and assessed in different clinical stages. Then, prostate cancer cell lines with low expression of ACACA were constructed to evaluate the changes in their cell cycle, proliferation, and metabolites. The effect of ACACA on tumor formation in vivo was analyzed. Also, mito-ATP production, mitochondrial staining, and mtDNA, nicotinamide adenine dinucleotide (NAD+/NADH), and reactive oxygen species (ROS) levels were detected. Results: ACACA was expressed more strongly in prostate cancer tissues. The expression level of ACACA was higher in patients with advanced PCa than in patients with lower grades. The proliferation ability reduced in ACACA-knockdown cells. In in vivo tests, the tumor volume and weight were lower in the experimental group than in the control group. Mito-ATP production decreased significantly after ACACA suppression, mtDNA levels and MitoTracker staining decreased in the experimental group. The ratio of NAD+/NADH and ROS levels were upregulated in the experimental group. Conclusion: Targeting ACACA gene and mitochondria might serve as a novel therapy for prostate cancer treatment.

Summed rest score in gated myocardial perfusion imaging is a good predicator for treatment-related cardiotoxicity after anthracycline chemotherapy in patients with diffuse large B-cell lymphoma.

Anthracycline chemotherapy is commonly used in the treatment of diffuse large B-cell lymphoma (DLBCL). Treatment-related cardiotoxicity (TRC) is defined as when the patient is identified to have one of the following clinical manifestations: Symptomatic heart failure, cardiac death, arrhythmia, infarction, a decrease in left ventricular ejection fraction (LVEF) of >15% from baseline or a decrease in LVEF of >10 to <50%. TRC may induce severe cardiac failure or cardiac arrhythmia as the main cause of death. The present study aimed to investigate the prognostic value of the summed rest score (SRS) in gated myocardial perfusion imaging (G-MPI) for the early detection of TRC caused by anthracycline chemotherapy in patients with DLBCL. A total of 36 DLBCL patients were enrolled in the present study, and a series of parameters were compared at baseline and after chemotherapy. According to the occurrence of TRC during the observation period, the patients were divided into two groups, and parameters associated with cardiac function were compared. The SRS in G-MPI and the corrected QT interval in the electrocardiogram were significantly different before and after chemotherapy (P=0.012 and P=0.015, respectively). By comparing parameters associated with cardiac function between the TRC group (n=22) and the no-TRC group (n=14), it was found that only SRS was significantly different (P=0.012). Multivariate logistic regression analysis showed that the SRS level was the only independent predicator for TRC (P=0.018; HR, 6.053; 95% CI, 1.364-26.869). Receiver operating characteristic curve analysis identified an optimal SRS cutoff of >1 for predicting TRC after anthracycline chemotherapy (P<0.001). Overall, the G-MPI SRS level was an early indicator for TRC surveillance in patients with DLBCL after anthracycline chemotherapy. The application of G-MPI SRS in clinical practice may contribute to early treatment and a subsequent decrease in mortality caused by such cardiovascular complications.

Successful Treatment of a Patient with Chronic Myelogenous Leukemia with Concurrent Janus Kinase 2 (JAK2) R795S Mutation and Breakpoint Cluster Region-ABL1 (BCR-ABL1) Fusion: A Case Report and Literature Review.

BACKGROUND Although the V617F mutation in the Janus kinase 2 (JAK2) gene and the breakpoint cluster region-abl1 (BCR-ABL1) oncogene fusion have been considered mutually exclusive in most myeloproliferative neoplasms (MPNs), many recent studies have described patients with both. This report describes a patient with chronic myelogenous leukemia (CML) and the unusual JAK2 R795S mutation and reviews 23 additional patients with JAK2 gene mutations coexisting with myelofibrosis (MF) and CML. CASE REPORT A 50-year-old woman with MF experienced rapid disease progression 3 weeks later, accompanied by severe abdominal pain and a white blood cell count of 257.45×109/l. Karyotype analysis indicated that she was 46, XY, Philadelphia (Ph) (+) and BCR-ABL1 positive. Bone marrow aspiration after 1 cycle of chemotherapy and treatment with dasatinib showed that her marrow was hypercellular, with an increased number of megakaryocytes and 48.5% myeloblasts expressing the myeloid antigens CD33, CD13, CD34, CD117, and CD71. Next-generation sequencing identified a rare JAK2 R795S mutation. She was diagnosed with CML in blast phase, and was successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). CONCLUSIONS JAK2 gene mutations, including the rare JAK2 R795S mutation, can coexist with BCR-ABL1 in patients with MPNs. The clinical course of MPN in patients with both BCR-ABL1 and JAK2 mutations may be different from that in patients with classical MPNs.

Carbon Nanospheres Exert Antitumor Effects Associated with Downregulation of 4E-BP1 Expression on Prostate Cancer.

INTRODUCTION: Although carbon nanospheres (CNPs) are promising nanomaterials in cancer treatment, how they affect prostate cancer (PCa) remains unclear. METHODS: In this study, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy were used to confirm the successful synthesis of CNPs. CCK-8, flow cytometry, Transwell, wound healing, Western blot and immunohistochemistry (IHC) assays were performed to evaluate the antitumor effect of CNPs toward the two kinds of prostate cancer cell lines PC3 and DU145. RESULTS: Our results showed that CNPs inhibited cell growth, invasion, and migration and induced apoptosis and autophagy in PCa cells. Multifactor detection of a single Akt phosphorylation pathway and Western blot results suggested the suppression of 4E-BP1 in PCa cells after incubation with CNPs. The results from animal experiments also suggested the antitumor effect of CNPs and reduced 4E-BP1 expression in PCa tissue samples from BALB/c nude mice administered a local subcutaneous injection of CNPs.

Decitabine and all-trans retinoic acid synergistically exhibit cytotoxicity against elderly AML patients via miR-34a/MYCN axis.

This study aimed to investigate the efficacy and mechanism of decitabine (DAC) and all-trans retinoic acid (ATRA) in elderly acute myeloid leukemia (AML) patients and cultured cells. Our clinical trial enrolled 36 elderly patients who were judged ineligible for conventional chemotherapy, receiving DAC and ATRA regimen (DAC 20 mg/m2 days 1-5; ATRA 20 mg/m2 days 4-28 in the first cycle and days 1-28 in the subsequent cycle). Treated with a median of 3 cycles (range 1-6), 44.4 % of patients achieved complete remission (CR), 11.1 % achieved CR with incomplete peripheral count recovery (CRi) and 13.9 % achieved partial remission (PR). The median overall survival (OS) was 12.1 months; the 1-year and 2-year OS rates were 49.6 % and 17.2 %. In addition, our in vitro studies indicated that the antineoplastic activities of DAC and ATRA mutually reinforced, which induced growth inhibition, cell cycle arrest and apoptosis of AML cells. Meanwhile, we found DAC and ATRA inhibited DNMT1, activated miR-34a via promoter hypomethylation, down-regulated its target MYCN and thus exerted a synergistic antineoplastic effect. In conclusion, DAC plus ATRA regimen might be effective and well-tolerated for elderly patients partially through modulating miR-34a/MYCN axis.

An Atypical PML-RARA Rearrangement Resulting from Submicroscopic Insertion of the RARA Gene at the PML Locus with Novel Breakpoints within PML Exon 7b and RARA Exon 3.

The diagnostic hallmark of acute promyelocytic leukemia (APL) is the reciprocal translocation t(15;17), resulting in the characteristic PML-RARA fusion; however, patients occasionally have masked PML-RARArearrangements. We report an APL case with no evidence of t(15;17) or PML-RARA rearrangement by karyotype or commercial reverse transcription polymerase chain reaction analyses. Fluorescence in situ hybridization detected a small RARA insertion signal within PML. mRNA sequencing identified a novel PML-RARA transcript generated from the juxtaposition of PMLIIa (exons 1-4, 6, and 7ab) and RARA exons (3-9), with novel breakpoints in PML exon 7b and RARA exon 3. The patient achieved molecular remission after the second consolidation chemotherapy and remains in complete remission 22 months after initial presentation. This is the first report of an APL case presenting with submicroscopic ins(15;17) and simultaneous novel breakpoints in both PML and RARA. This case highlights the importance of sequence analysis to confirm APL diagnosis and for subsequent monitoring of minimal residual disease.

Decitabine combined with all-trans retinoic acid as treatment in a case of primary myelofibrosis transforming into acute myeloid leukaemia.

Primary myelofibrosis (PMF) is a type of cloned myeloproliferative neoplasm stemming from haematopoietic stem cells, and tends to transform to acute myeloid leukaemia (AML) in approximately 10-20% of cases over a 10-year period. The transformation into AML has a poor prognosis, with a median overall survival of only 2.6 months in patients receiving supportive treatment. To date, treatment of AML transformation remains poor. The case of a 58-year-old female patient with AML transformed from PMF, who was treated with decitabine combined with all-trans retinoic acid, is reported. The patient had complete remission and a 17-month overall survival from initial diagnosis of transformed AML, with tolerated haematologic toxicity during the treatment period.