Efficacy and safety of pomalidomide and low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma: a multicenter, prospective, single-arm, phase 2 trial.

BACKGROUND: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. METHODS: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). RESULTS: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. CONCLUSIONS: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. TRIAL REGISTRATION: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial.

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.

LncRNA FIRRE is activated by MYC and promotes the development of diffuse large B-cell lymphoma via Wnt/ß-catenin signaling pathway.

Diffuse large B-cell lymphoma (DLBCL) contributes to the cancer-related mortality. Increasing evidence have reported the crucial role of long non-coding RNAs (lncRNAs) in tumorigenesis. Microarray analysis was used to screen out the differentially expressed lncRNAs. qRT-PCR proved that lncRNA functional intergenic repeating RNA element (FIRRE) was up-regulated in DLBCL tissues and cells. Based on Kaplan-Meier analysis, high FIRRE level was associated with the poor overall survival. Subsequently, cell functional assays further revealed that FIRRE functioned as an oncogene by promoting cell proliferation and reducing cell apoptosis in DLBCL. The upstream mechanism of FIRRE was analyzed in accordance with the bioinformatics analysis and mechanism experiments. The results showed that MYC proto-oncogene (MYC) contributed to the transcriptional activation of FIRRE in DLBCL cells. Further mechanism investigation prompted us to determine the association between Wnt/ß-catenin signaling pathway and FIRRE. Subcellular fractionation assay and western blot assay demonstrated that FIRRE activated Wnt/ß-catenin signaling pathway by promoting nuclear translocation of ß-catenin. Taken together, FIRRE activated Wnt/ß-catenin signaling pathway to facilitate DLBCL cell growth via modulation of the nuclear translocation of ß-catenin. Our findings reveals the novel molecular mechanism of FIRRE in DLBCL.

Low platelet count as risk factor for infections in patients with primary immune thrombocytopenia: a retrospective evaluation.

Infectious complications are common and sometimes life threatening in patients with immune thrombocytopenia (ITP), mainly due to the immune-suppressive therapy. Recent evidence suggests a potential role of platelets in the inflammation process. In this clinical study, we further investigated the role of thrombocytopenia on infections in patients with primary ITP. We retrospectively evaluated data from the recently published large randomized clinical trial of a cohort of 195 patients with primary ITP, who were randomized for prednisone or high-dose dexamethasone. From 158 patients (81%), data on platelet count and infections within the first month of treatment were collected. In this period, 24% of the ITP patients had an infection. Patients with infection had significant lower platelet counts during the first month of treatment leading to a significant lower therapy response at 1 month and a significant longer hospital stay (14.0 versus 9.8 days). Additionally, Cox regression analysis showed that an increase in platelet count of 20 × 109/L led to a reduction of 52% in infections in the next week, showing low platelet count is a significant risk factor for infection. Platelet transfusion led to an increase in platelet count in ITP patients without infection, but not in patients with infection. In conclusion, infections are common in patients with primary ITP leading to significant worse response rates and a longer hospital stay. Interestingly, low platelet count was independently correlated with an increased risk of infection.

A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP.

This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.

Effectiveness of estrogen treatment before transcervical resection of adhesions on moderate and severe uterine adhesion patients.

Intrauterine adhesion (IUA), also known as Asherman's syndrome, is a common disease for among women. The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity. This current study investigates the association of different doses of estrogen before transcervical resection of adhesions (TCRA) surgery and clinical outcome in serious IUA. About 120 newly diagnostic serious IUA patients who underwent TCRA were randomly divided into three study groups: Estradiol valerate (progynova) 3 or 9 mg per diet before surgery and the control group. Follow-up hysteroscopy checkups were taken in 1- and 3-month post-operation. The effective power of 9 mg group was significantly higher than other groups. The 9 mg group achieved the best menstrual recovery rate in all study groups compared with the other two groups in 6 months post-operatively (p < 0.05). Our results confirmed estradiol valerateas an alternative effective drug for the prevention of IUAs before and after hysteroscopic surgery.

Gynecomastia in a Chronic Myeloid Leukemia Patient After Switching from Imatinib to Flumatinib.

Gynecomastia refers to the abnormal enlargement of the male breast caused by the proliferation of the glandular component of the breast, typically due to sexual hormone disturbance. Multiple medications have been linked to the development of gynecomastia with varying incidences. This adverse event has also been associated with TKIs such as imatinib, dasatinib, and rarely nilotinib. However, it is poorly described and regarded as a rare event. Herein, we present the first case of a CML patient who developed gynecomastia after switching from imatinib to flumatinib. The patient is an 82-year-old male. He was diagnosed with CML and initially treated with imatinib. However, the treatment response milestone after three months of imatinib was not achieved. Hence, flumatinib was used to replace imatinib. Unexpectedly, two weeks later, he developed gynecomastia. Gynecomastia usually causes distress to patients, and there are currently no clear mechanisms or management strategies for this condition. Inspired by this case and through a review of the literature, we propose possible mechanisms and management strategies for this rare adverse event associated with TKIs, along with future perspectives. This may assist others in dealing with this issue and stimulate research on it.

Bone marrow necrosis: Facts, controversies, and perspective.

Bone marrow necrosis (BMN) is a clinically and pathologically poorly-defined and readily-overlooked entity. The current facts and guidelines pertaining to this entity are scarce, and there exist controversies. Upon reviewing the literature, we present the facts, analyze these controversies, and discourse on future prospects.

Transformation of Severe Aplastic Anemia into Donor Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Rare Case Report.

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for severe aplastic anemia (SAA). It is known that SAA can evolve into malignant clonal diseases, such as acute myeloblastic leukemia (AML) or myelodysplastic syndrome. However, the transformation of SAA into AML after allo-HSCT is a rare phenomenon. Here, we report a case of SAA transformed into AML after patient received human leucocyte antigen (HLA)-matched sibling peripheral blood stem cell transplantation. CASE REPORT A 51-year-old female patient presented with petechiae and fatigue and received a diagnosis of idiopathic SAA. The immunosuppressive therapy combined with umbilical cord blood transplantation failed for this patient. Then, she received HLA-matched sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). However, 445 days after allo-PBSCT, the patient had a diagnosis of AML by bone marrow puncture. Donor-recipient chimerism monitoring and cytogenetic analysis confirmed that the leukemia was donor cell origin. Notably, a new HOXA11 mutation was detected in the peripheral blood of the patient after transplantation by whole-exome sequencing, which was the same gene mutation detected in the donor. The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission. However, the leukemia relapsed after 2 cycles of consolidation chemotherapy. Unfortunately, the patient died of leukemia progression 575 days after allo-HSCT. CONCLUSIONS The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy.

Prediction of myofascial pelvic pain syndrome based on random forest model.

Objective: The objective is to construct a random forest model for predicting the occurrence of Myofascial pelvic pain syndrome (MPPS) and compare its performance with a logistic regression model to demonstrate the superiority of the random forest model. Methods: We retrospectively analyze the clinical data of female patients who underwent pelvic floor screening due to chronic pelvic pain at the Pelvic Floor Rehabilitation Center of the Third Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. A total of 543 female patients meeting the study's inclusion and exclusion criteria are randomly selected from this dataset and allocated to the MPPS group. Furthermore, 702 healthy female patients who underwent pelvic floor screening during routine physical examinations within the same timeframe are randomly selected and assigned to the non-MPPS group. Chi-square test and rank-sum test are used to select demographic variables, pelvic floor pressure assessment data variables, and modified Oxford muscle strength grading data for logistic univariate analysis. The selected variables are further subjected to multivariate logistic regression analysis, and a random forest model is also established. The predictive performance of the two models is evaluated by comparing their accuracy, sensitivity, specificity, precision, receiver operating characteristic (ROC) curve, and area under the curve (AUC) area. Results: Based on a dataset of 1245 cases, we implement the random forest algorithm for the first time in the screening of MPPS. In this investigation, the Logistic regression model forecasts the accuracy, sensitivity, specificity, and precision of MPPS at 69.96 %, 57.46 %, 79.63 %, and 68.57 % respectively, with an AUC of the ROC curve at 0.755. Conversely, the random forest prediction model exhibits accuracy, sensitivity, specificity, and precision rates of 87.11 %, 90.66 %, 90.91 %, and 83.51 % respectively, with an AUC of the ROC curve at 0.942. The random forest model showcases exceptional predictive performance during the initial screening of MPPS. Conclusion: The random forest model has exhibited exceptional predictive performance in the initial screening evaluation of MPPS disease. The development of this predictive framework holds significant importance in refining the precision of MPPS prediction within clinical environments and elevating treatment outcomes. This research carries profound global implications, given the potentially elevated misdiagnosis rates and delayed diagnosis proportions of MPPS on a worldwide scale, coupled with a potential scarcity of seasoned healthcare providers. Moving forward, continual refinement and validation of the model will be imperative to further augment the precision of MPPS risk assessment, thereby furnishing clinicians with more dependable decision-making support in clinical practice.

Prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma: Further risk stratification of the group with low-risk and high-risk NCCN-IPI.

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma (DLBCL) and the prognostic value of them in the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) subgroups. METHODS: A total of 113 patients who underwent 18F-FDG PET/CT examination in our institution were retrospectively collected. The MTV was measured by iterative adaptive algorithm. The location of the lesion was obtained according to its three-dimensional coordinates, and Dmax was obtained. SDmax is derived from Dmax standardized by body surface area (BSA). The X-tile method was used to determine the optimal cut-off values for MTV, Dmax and SDmax. Cox regression analysis was used to perform univariate and multivariate analyses. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: The median follow-up time was 24 months. The median of MTV was 196.86 cm3 (range 2.54-2925.37 cm3), and the optimal cut-off value was 489 cm3. The median of SDmax was 0.25 m-1 (range 0.12-0.51 m-1), and the best cut-off value was 0.31 m-1. MTV and SDmax were independent prognostic factors of PFS (all P < 0.001). Combined with MTV and SDmax, the patients were divided into three groups, and the difference of PFS among the groups was statistically significant (P < 0.001), and was able to stratify the risk of NCCN-IPI patients in the low-risk (NCCN-IPI < 4) and high-risk (NCCN-IPI ≥ 4) groups (P = 0.001 and P = 0.031). CONCLUSION: MTV and SDmax are independent prognostic factors for PFS in DCBCL patients, which describe tumor burden and tumor dissemination characteristics, respectively. The combination of the two could facilitate risk stratification between the low-risk and high-risk NCCN-IPI groups.

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

BACKGROUND: The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS). METHODS: In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m2 /day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m2 /day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles. RESULTS: The median follow-up was 14 months (range 2-36). The primary end point of overall response rate in the intent-to-treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294). CONCLUSION: The 5-day 20-mg/m2 /day and 8-day 12-mg/m2 /day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS.

Disseminated fusarium infection after allogeneic hematopoietic stem cell transplantation after CART: A case report.

BACKGROUND: Fusarium is a conditional pathogen that can cause invasive infection in patients with hematological diseases under immune function. METHODS: A case of recurrent and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia was treated with allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor-modified T cells treatment. RESULTS: During transplantation, disseminated Fusarium infection occurred, involving the skin, liver, spleen and central nervous system, and the patient eventually died. CONCLUSIONS: Early identification of Fusarium infection based on the characteristic rash and timely antifungal treatment can improve the cure rate.

Characteristic features of primary testicular lymphoma and survival trends: a multicenter clinical study.

OBJECTIVES: To retrospectively investigate the clinical characteristics, prognosis, treatment, and therapy outcome of Chinese patients with primary testicular lymphoma (PTL). METHODS: we collected data of 49 PTL patients from four hospitals over 13 years. The median age was 63 years old. We described the clinical characteristics of the patients including the laterality, serum lactate dehydrogenase (LDH), pathology classification, stage, International prognostic index (IPI) scores and more. RESULTS: Complete remission (CR) was achieved in 34 patients and partial remission (PR) in 3 patients; Progressive disease (PD) was detected in 11 patients, and 10 patients died. The average progression-free survival (PFS) of all patients was 43.92 months, and the average overall survival (OS) was 47.55 months. The Ann Arbor stage, IPI score, and LDH were associated with OS, while Ann Arbor stage, IPI score, LDH, and histotype were significantly associated with PFS. Chemotherapy and radiotherapy following orchiectomy was associated with a significantly longer PFS. CONCLUSION: Most patients can achieve CR after induced therapy or orchiectomy. However, there are many associated prognostic factors.

[The efficacy and safety of 2 cycles' high-dose dexamethasone treatment adult primary immune thrombocytopenia].

OBJECTIVE: To investigate the efficacy and safety of a schedule of 2 cycles' high-dose dexamethasone (HD-DXM) as an initial therapy in adults immune thrombocytopenia (ITP), and compare with conventional dose prednisone therapy. METHOD: A total of 59 newly diagnosed ITP patients were divided into 2 groups randomly. In 30 patients (Dexamethasone group), oral HD-DXM was administered at 40 mg/d for 4 consecutive days, repeated one week later, and then failed to maintain. In the remaining 29 patients (Prednisone group), prednisone was administered orally at 1.0 - 1.5 mg×kg(-1)×d(-1) for 4 weeks, and then gradually tapered. RESULTS: For short-term efficacy, after 1 and 2 weeks of treatment, the response rate in Dexamethasone group was significantly higher than that in Prednisone group (50.0% vs 24.1%, P < 0.01; 73.3% vs 55.2%, P < 0.05), while 3 weeks later, there was no remarkable difference between the two groups (83.3% vs 68.9%, P > 0.05), though the response rate in Dexamethasone group remained higher. For long-term effect, at the end of the 2nd and 3rd months of follow-up, the relapse rate in Dexamethasone group was significantly lower than that in Prednisone group (24.0% vs 40.0%, P < 0.05; 32.0% vs 65.0%, P < 0.01), while at the end of the 1(st) month of follow-up, there was no significant difference (16.0% vs 20.0%, P > 0.05). In addition, it's well tolerated and no complications such as severe infection or Cushing syndrome were complained in Dexamethasone group. CONCLUSION: HD-DXM possesses an advantage over conventional dose prednisone therapy in efficacy and safety.

Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.

BACKGROUND: Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia. METHODS: This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 109 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 109 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 109 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 109 cells per L but less than 100 × 109 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626. FINDINGS: From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths. INTERPRETATION: Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response. FUNDING: National Natural Science Foundation of China.

MicroRNA-21 and microRNA-155 promote the progression of Burkitt's lymphoma by the PI3K/AKT signaling pathway.

INTRODUCTION: Burkitt's lymphoma (BL) is a rare and highly aggressive B cell non-Hodgkin lymphoma. High toxicity of chemotherapy for BL treatment causes morbidity and mortality. Many miRNAs have been used as biomarkers for early detection or therapy targets for tumors. However, the roles of miR-21 and miR-155 in Burkitt's lymphoma remain unclear. METHODS: We collected 15 blood samples from patients with Burkitt's lymphoma and evaluated the expression of miR-21 and miR-155. Then, we knocked down miR-21 and miR-155 expression in Burkitt's lymphoma cell lines and assessed cell proliferation, cell cycle, and apoptosis. Furthermore, we detected the activation of PI3K/AKT pathway by qPCR and western blot. Finally, we predicted the target genes of miR-21 and miR-155 by publicly available databases. RESULTS: The expression of miR-21 and miR-155 in blood samples from patients with Burkitt's lymphoma were significantly upregulated. Knockdown of miR-21 and miR-155 significantly suppressed cell proliferation, and resulted in S phase arrest and cell apoptosis. The knockdown of miR-21 and miR-155 inhibited the activation of the PI3K/AKT pathway. We found that the target genes of miR-21 and miR-155 were C1RL and TCAP. CONCLUSION: miR-21 and miR-155 promote the progression of Burkitt's lymphoma through PI3K/AKT signaling by targeting C1RL and TCAP. Our findings will provide a novel biomarker and therapeutic strategies for Burkitt's lymphoma.

Acquired aplastic anemia: Is bystander insult to autologous hematopoiesis driven by immune surveillance against malignant cells?

We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations (GCPs). This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments, with each recurrence occurring 7-8 wk from a GCP. After his third recurrence, he was prescribed successive treatment with rifampicin, berberine, and monthly administered GCP for 4 mo, and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy, and eventually died of septic shock. Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis. From the treatment process and laboratory investigations, it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state. Incorporation of rifampicin, berberine, and monthly GCP into cyclosporine can enhance the immunosuppressive effect. In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure, the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.