Generation of a new therapeutic D-peptide that induces the differentiation of acute myeloid leukemia cells through A TLR-2 signaling pathway.

Acute myeloid leukemia (AML) is caused by clonal disorders of hematopoietic stem cells. Differentiation therapy is emerging as an important treatment modality for leukemia, given its less toxicity and wider applicable population, but the arsenal of differentiation-inducing agents is still very limited. In this study, we adapted a competitive peptide phage display platform to search for candidate peptides that could functionally induce human leukemia cell differentiation. A monoclonal phage (P6) and the corresponding peptide (pep-P6) were identified. Both L- and D-chirality of pep-P6 showed potent efficiency in inducing AML cell line differentiation, driving their morphologic maturation and upregulating the expression of macrophage markers and cytokines, including CD11b, CD14, IL-6, IL-1ß, and TNF-α. In the THP-1 xenograft animal model, administration of D-pep-P6 was effective in inhibiting disease progression. Importantly, exposure to D-pep-P6 induced the differentiation of primary human leukemia cells isolated AML patients in a similar manner to the AML cell lines. Further mechanism study suggested that D-pep-P6 induced human leukemia cell differentiation by directly activating a TLR-2 signaling pathway. These findings identify a novel D-peptide that may promote leukemia differentiation therapy.

CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication after transplantation. The purpose of this study was to examine the incidence and risk factors for HC after hematopoietic stem cell transplantation (HSCT). The records of patients who underwent allogenic HSCT from January 2012 to December 2018 at our institution were retrospectively reviewed. Cox proportional regression and Kaplan-Meier analyses were performed to determine independent risk factors for HC. The statistical analysis was performed in May 2020. A total of 173 patients underwent HSCT, and 53 (30.6%) developed grade 2 or 3 HC cystitis at a median of 37 days (range - 5 to 98 days) after transplantation. Thirty-two patients developed moderate (grade 2) cystitis and 21 severe (grade 3) cystitis. Of the 173 patients, 61 developed acute graft-versus-host disease (GVHD) (median onset day 24) and 79 experienced cytomegalovirus (CMV) reactivation (median onset day 35). The relative risk (RR) of developing a CMV infection for patients with acute GVHD was 2.77 times that of patients without acute GVHD (P < 0.001). CMV infection was the only independent variable significantly associated with HC in both univariate and multivariate analyses. The estimated hazard ratio (HR) of CMV infection for the development of HC was 5.57 (95% confidence interval [CI]: 2.52 to 12.33, P < 0.001). CMV infection is an independent risk factor for the development of HC after HSCT, and acute GVHD is a risk factor for CMV reactivation. Decreasing the frequency of GVHD after HSCT may result in a lower frequency of HC.

Bone Marrow Mesenchymal Stem Cells-Derived Exosomal miR-425-5p Inhibits Acute Myeloid Leukemia Cell Proliferation, Apoptosis, Invasion and Migration by Targeting WTAP.

INTRODUCTION: Acute myeloid leukemia (AML) is a predominant blood malignancy with high mortality and severe morbidity. AML is affected by microRNAs (miRNAs) loaded in exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs). MiR-425-5p has been reported to participate in different cancer models. However, the function of BM-MSCs-derived exosomal miR-425-5p in AML is unclear. METHODS: The expression of miR-425-5p was measured by qRT-PCR in clinical AML samples. The immunophenotype of BM-MSCs was analyzed using antibodies against CD44, CD90, and CD105. The exosome was isolated from BM-MSCs. The effect of BM-MSCs-derived exosomal miR-425-5p on AML was analyzed by CCK-8 assay, Edu assay, transwell assay, flow cytometry in AML cells. qRT-PCR, luciferase reporter gene assay and Western blot analysis were also conducted in AML cells. RESULTS: The expression levels of miR-425-5p were decreased in CD34 + CD38-AML cells from primary AML patients compared to that from the bone marrow of healthy cases, and were reduced in exosomes from AML patients compared that from healthy cases. Similarly, miR-425-5p was also down-regulated in AML cell lines compared with BM-MSCs. MiR-425-5p was able to express in exosomes from BM-MSCs. CCK-8, Edu, transwell assay and flow cytometry analysis revealed that BM-MSCs-derived exosomal miR-425-5p significantly inhibited cell viability, Edu positive cells, invasion and migration, and induced apoptosis of AML cells. Meanwhile, the expression levels of cleaved PARP and cleaved caspase3 were increased by BM-MSCs-derived exosomal miR-425-5p in cells. MiR-425-5p inhibited the expression of Wilms tumor 1-associated protein (WTAP). Moreover, overexpression of WTAP could reverse the miR-425-5p-induced inhibition effect on AML cell proliferation, apoptosis, migration and invasion. CONCLUSION: BM-MSCs-derived exosomal miR-425-5p inhibits proliferation, invasion and migration of AML cells and induced apoptosis of AML cells by targeting WTAP. Therapeutically, BM-MSCs-derived exosomal miR-425-5p may serve as a potential target for AML therapy.

MicroRNA­93 knockdown inhibits acute myeloid leukemia cell growth via inactivating the PI3K/AKT pathway by upregulating DAB2.

Acute myeloid leukemia (AML) is associated with a poor prognosis in elderly adults and currently lacks optimal treatment strategies. MicroRNAs (miRNAs or miRs) have increasingly been reported to be associated with AML progression; however, the mechanisms of action of miR­93 in AML with the involvement of disabled 2 (DAB2) are currently unknown. In the present study, miR­93 expression was assessed in patients with AML and in AML cell lines. The association between miR­93 expression and the pathological characteristics of patients with AML was analyzed. AML cells were then transfected to knockdown or overexpress miR­93 in order to elucidate its function in AML progression. The target gene of miR­93 was assessed using a dual­luciferase reporter gene assay. The expression levels of miR­93, DAB2 and phosphatidylinositol 3­kinase (PI3K)/protein kinase B (AKT) pathway­related proteins were measured and in vivo experiments were conducted to confirm the results. It was observed that miR­93 was highly expressed in patients with AML and in AML cells. The knockdown of miR­93 in HL­60 cells inhibited AML cell proliferation and resistance to apoptosis, while the overexpression of miR­93 in THP­1 cells led to contrasting results. Moreover, miR­93 targeted DAB2 to inactivate the PI3K/AKT pathway, and the overexpression of DAB2 reversed the effects of miR­93 on THP­1 cell growth. Tumor volume, tumor weight, and the positive expression of Ki67, survivin and p53 were increased in THP­1 cells overexpressing miR­93. On the whole, the present study demonstrates that miR­93 is highly expressed in AML cells, and that the suppression of miR­93 inhibits AML cell growth by targeting DAB2 and inhibiting the PI3K/AKT pathway.

A Regulatory Loop Involving Notch and Wnt Signaling Maintains Leukemia Stem Cells in T-Cell Acute Lymphoblastic Leukemia.

Leukemia-initiating cells play critical role in relapse, resistance to therapies and metastases but the mechanism remains largely elusive. We report that ß-catenin is over-expressed in almost all T-ALL patients and flow sorted ß-cateninhigh fractions are highly resistant to therapy, leading to liver metastases in nude mice as well as dysregulated lncRNAs. Pharmacological inhibition through XAV-939 as well as si-RNA mediated inhibition of ß-catenin is initially effective in re-sensitization to therapy, however, prolonged inhibition shifts dependency from ß-catenin to Notch signaling, with particularly high levels of receptors Notch 1 and Notch 2. The results are verifiable in a cohort of T-ALL patients comprising of responders vs. those who have progressed, with ß-catenin, Notch 1 and Notch 2 elevated in progressed patients. Further, in patients-derived cells, silencing of Notch 1 or Notch 2 does not counter resistance to ß-catenin inhibition, rather pharmacological pan-Notch inhibition is needed to overcome resistance and its effect on in vitro tumor sphere formations as well as in vivo liver metastases. Thus, wnt and Notch signaling are part of a regulatory loop mutually compensating for each other in T-ALL, while ensuring the maintenance of stem cell phenotype.

MiR-335-3p inhibits cell proliferation and induces cell cycle arrest and apoptosis in acute myeloid leukemia by targeting EIF3E.

Here, we aimed to investigate the biological roles and the regulatory mechanisms of miR-335-3p in acute myeloid leukemia (AML). We first found miR-335-3p was significantly downregulated in blood samples from leukemia patients and cell lines using reverse transcription quantitative polymerase chain reaction. Through CCK-8 assay and flow cytometry, we observed that miR-335-3p overexpression significantly inhibited cell proliferation and induced cell cycle G0/G1 arrest and apoptosis in AML cell lines (THP-1 and U937). Moreover, miR-335-3p directly targets EIF3E and negatively regulated its expression. More importantly, EIF3E overexpression reversed the effects of miR-335-3p on cell proliferation, G1/S transition, and apoptosis. Furthermore, miR-335-3p overexpression obviously downregulated the expression of CDK4, Cyclin D1, and Bcl-2, while upregulated the expression of p21 and Bad, which were significantly rescued by the cotransfection of pcDNA3.1-EIF3E. Collectively, our study proposes that miR-335-3p/EIF3E axis could be a promising therapeutic target to mitigate the progression of AML.

An Immune Risk Score Predicts Survival of Patients with Acute Myeloid Leukemia Receiving Chemotherapy.

PURPOSE: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. EXPERIMENTAL DESIGN: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. RESULTS: Six flow cytometry-validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. CONCLUSIONS: Our immune risk score complements current AML prediction models.

Esophageal squamous cell cancer coincides with myelodysplastic syndrome/acute myelogenous leukemia: A case report and review of the literature.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors, and has high incidence and mortality rates, worldwide. Myelodysplastic syndrome (MDS), a disorder of hematopoietic stem or progenitor cells, results in marrow failure, which increases the risk of acute myeloid leukemia (AML). Few studies had reported patients who have suffered from both ESCC and MDS/AML simultaneously. To identify possible potential associations between ESCC and MDS/AML, the present case report describes a patient with both types of these tumors at the same time. Following endoscopic biopsy, the patient was revealed to have moderately differentiated SCC. MDS with excess blasts was subsequently diagnosed following bone marrow aspiration. The results of next-generation sequencing revealed that TP53 and ROS1 were both found in ESCC and MDS/AML tumors. The patient refused therapeutic intervention and died within 20 days. The current report demonstrated that hematologic malignancies presenting alongside solid tumors should be considered clinically. In addition, the report indicated that bone marrow puncture should be performed in patients with solid tumors and abnormal blood test results. Next-generation sequencing may be a useful technique for the investigation of patients with two or more neoplasms. However, more research regarding the co-existence of solid tumors with hematological malignancy are required.

High serum extracellular vesicle miR-10b expression predicts poor prognosis in patients with acute myeloid leukemia.

BACKGROUND: Increasing evidence have demonstrated that serum extracellular vesicle microRNAs (EV-miRNAs) are promising noninvasive biomarkers for various cancer types. OBJECTIVE: In this study, we aimed to investigate and evaluate the potential clinical significance of serum EV-miR-10b for acute myeloid leukemia (AML). METHODS: Blood samples were collected from a cohort of 95 de novo AML patients and 80 healthy individuals. Of all AML patients, 51 patients were considered as cytogenetic normal AML (CN-AML). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to measure the expression levels of serum EV-miR-10b. RESULTS: The extracellular vesicles we extracted from the serum samples were positive for EV/exosome markers including TSG101, CD63, Flotillin-1 and CD9. The expression levels of serum EV-miR-10b were significantly higher in AML/CN-AML patients than healthy controls. In addition, serum EV-miR-10b expression was strongly correlated with aggressive clinical characteristics. Moreover, receiver operating characteristic analysis showed serum EV-miR-10b yielded an area under the curve of 0.875, with 77.89% specificity and 82.50% sensitivity in identifying AML patients from normal controls. Furthermore, AML patients with higher serum EV-miR-10b expression had significantly shorter survival and serum EV-miR-10b was demonstrated to be an independent prognostic marker for overall survival in AML. CONCLUSIONS: Taken together, serum EV-miR-10b might serve as a promising biomarker for predicting the prognosis of AML.

CircRNA circ_0000190 inhibits the progression of multiple myeloma through modulating miR-767-5p/MAPK4 pathway.

BACKGROUND: Multiple myeloma (MM) accounts for 10% of all hematological malignancies. Dysregulation of microRNAs (miRNAs) or long non-coding RNAs (lncRNAs) has important impacts on progression of MM. Circular RNAs (circRNAs) are correlated with malignancy in the modulation of tumor progression. This study aims to investigate the effect of circ_0000190 on regulating the progression of MM. METHOD: Microscopic examination via single molecule fluorescent in situ hybridization indicates the location of circ_0000190. qRT-PCR and Western blot were used to evaluate the expression of RNAs and proteins. Potential target of circ_0000190 was searched as miRNA, and examined by luciferase reporter assay. A computational screen was also conducted to search the potential target of miRNA. In vitro cell viability, proliferation, apoptosis assays and flow cytometric were performed to assess the effects of circ_0000190 and its target on MM. Mice model of human MM was established with subcutaneous xenograft tumor, qRT-PCR and western blot were performed to detect the underlying mechanisms of circ_0000190 on MM. RESULTS: Circ_0000190 was located in the cytoplasm, and down-regulated in both bone marrow tissue and peripheral blood, while the target of circ_0000190, miR-767-5p, was up-regulated, suggesting a negative correlation between them. The binding ability between circ_0000190 and miR-767-5p was confirmed by luciferase reporter assay. Moreover, circ_0000190 inhibited cell viability, proliferation and induced apoptosis of MM thus inhibiting cell progression, which is partially through the negative regulation of miR-767-5p. Mitogen-activated protein kinase 4 (MAPK4) is a direct target of miR-767-5p. In addition, over-expression of miR-767-5p promoted cell progression by directly targeting and regulating MAPK4. The MM model mice with administration of circ_0000190 suppressed tumor growth and progression. CONCLUSION: Our results revealed that the ability of circ_0000190 to protect against MM was inherited through repression of miR-767-5p, and miR-767-5p might be a tumor drive through targeting MAPK4. Therefore, a novel role of circ_0000190 on regulating the progression of MM was found, and the clinical application of circRNAs might represent a strategy in MM.

PRDX6 promotes proliferation and induces chemo-resistance via peroxidase activity in Toledo diffuse large B-cell lymphoma cells.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphomas. Despite the application of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen being effective on 70-80% of DLBCL patients, the remaining 20-30% develop an even more aggressive relapsed tumor. PRDX6 has been shown to play important roles in multiple cancers. However, there is no study about the role of PRDX6 in DLBCL. METHODS: The stable Toledo cell lines that overexpression or knockdown of PRDX6 gene were established. Western blot was used to determine the quantity of PRDX6 protein. Then, the function of PRDX6 in Toledo cell proliferation was determined using cell counting assay and Annexin V/PI analysis assays, and the underlying mechanism was determined through glutathione peroxidase activity and iPLA2 activity assay. RESULTS: In the current study, we showed that the expression of PRDX6 was critical for the proliferation of Toledo DLBCL cells. Additionally, knockdown of PRDX6 induced apoptosis in Toledo DLBCL cells. Importantly, overexpression of PRDX6 caused a doxorubicin resistance in Toledo DLBCL cells, while downregulation of PRDX6 significantly enhanced doxorubicin induced apoptosis. Interestingly, the glutathione peroxidase activity of PRDX6, but not the phospholipase A2 activity, was crucial for PRDX6 induced proliferation and anti-apoptosis effects. Together, our study explored the tumor promoting function of PRDX6 in DLBCL for the first time. CONCLUSIONS: Our data indicated that PRDX6 could be a target for overcoming drug resistance. Targeting PRDX6 expression or peroxidase activity could be an effective strategy to overcome drug resistance in clinical DLBCL treatment.

A Case of Unicentric Castleman Disease and Langerhans Cell Histiocytosis: Two Entities in One Lymph Node.

Background: Castleman disease (CD) is a lymphoproliferative disorder and Langerhans cell histiocytosis (LCH) is a clonal disease of the monocyte-macrophage system. The authors describe a rare case of CD coexistent with LCH at diagnosis in one lymph node. Methods: Hematologic investigation and intrapulmonary mass biopsy were performed. Results: The patient achieved complete remission and, up to now, no signs of recurrence were found. Conclusions: The report about co-existence with CD and LCH will promote correct diagnosis because of the recognition of this rare morphologic combination. An adequate amount of tissue should be obtained to avoid missing the diagnosis.

Knockdown of Long Noncoding RNA HOXA-AS2 Suppresses Chemoresistance of Acute Myeloid Leukemia via the miR-520c-3p/S100A4 Axis.

BACKGROUND/AIMS: Among different molecular candidates, there is growing data to support that long noncoding RNAs (lncRNAs) play a significant role in acute myeloid leukemia (AML). HOXA-AS2 is significantly overexpressed in a variety of tumors and associated with anti-cancer drug resistance, however, little is known regarding the expression and function of HOXA-AS2 in the chemoresistance of AML. In this study, we aimed to determine the role and molecular mechanism of HOXA-AS2 in adriamycin-based chemotherapy resistance in AML cells. METHODS: Quantitative real-time PCR was used to detect HOXA-AS2 expression in the BM samples and ADR cell lines, U/A and T/A cells. Furthermore, the effects of HOXA-AS2 silencing on cell proliferation and apoptosis were assessed in vitro by CCK8 and flow cytometry, and on tumor growth in vivo. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in AML. RESULTS: In this study, we showed that HOXA-AS2 is significantly upregulated in BM samples from AML patients after treatment with adriamycin-based chemotherapy and in U/A and T/A cells. Knockdown of HOXA-AS2 inhibited ADR cell proliferation in vitro and in vivo and promoted apoptosis. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay and anti-Ago2 RIP assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in ADR cells. S100A4 was predicted as a downstream target of miR-520c-3p, which was confirmed by luciferase reporter assay. CONCLUSION: Our results suggest that HOXA-AS2 plays an important role in the resistance of AML cells to adriamycin. Thus, HOXA-AS2 may represent a therapeutic target for overcoming resistance to adriamycin-based chemotherapy in AML.

Rapidly Progressive, Fata Infection Caused by Bacillus Cereus in a Patient with Acute Lymphoblastic Leukemia.

BACKGROUND: We herein report a fatal case of fulminant septicemia caused by Bacillus cereus in a 49-year-old female with T-cell acute lymphoblastic leukemia receiving chemotherapy. METHODS: Her two blood culture sets were positive for Gram-positive, rod-shaped bacterium. Bacillus cereus was identified by high-throughput MALDI-TOF mass spectrometry and 16S ribosomal RNA gene sequencing. RESULTS: The patient died within 12 hours from the onset of B cereus infection. CONCLUSIONS: Patients with acute leukemia presented with fever and unexplained multiple organ lesions, especially accompanied by CNS symptoms, should alert to the possibility of Bacillus cereus infection.

Multiple Nonleukemic Myeloid Sarcoma Associated Hemophagocytic Lymphohistiocytosis in an Adult.

BACKGROUND: Nonleukemic myeloid sarcoma (MS) occurs rarely. Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal condition. We report a rare case of nonleukemic MS associated with HLH. METHODS: Hematologic investigation, 18F-FDG PET/CT, bone marrow aspirate and biopsy, and lymph node biopsy were performed in a 25-year-old male patient. RESULTS: The patient was given a short-term treatment of etoposide and dexamethasone to control HLH. Then he received chemotherapy and responded well. CONCLUSIONS: It is important to find the underlying cause of HLH in high-risk patients. HLH can occur secondary to nonleukemic MS. Early diagnosis and treatment can improve survival.

Acute promyelocytic leukaemia with a PML-RARA insertional translocation and a chromosome 21 abnormality in XYY syndrome: case report.

The concomitant presence of the XYY syndrome with haematological malignancies is rare. This report presents a case of acute promyelocytic leukaemia (APL) with the promyelocytic leukaemia-retinoic acid receptor alpha (PML-RARA) gene insertional translocation and a chromosome 21 abnormality in a 29-year-old XYY male patient. Karyotype analysis revealed an abnormal karyotype of 47,XYY [14]/46,XYY,-21[16]. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analysis showed the existence of a PML-RARA fusion gene. The patient was treated by all-trans retinoic acid (ATRA) and chemotherapy. Laboratory results revealed that the coagulopathy improved and the patient achieved complete remission, based on bone-marrow morphology. The patient then received sequential monthly therapy using arsenic trioxide, followed by ATRA, followed by chemotherapy; he has survived disease-free for 36 months. Our findings suggest that the additional chromosomal abnormalities involving the sex chromosomes and chromosome 21 did not affect the prognosis of APL, and that the sequential treatment strategy had a good clinical effect without being associated with severe side-effects.

ATO/ATRA/anthracycline-chemotherapy sequential consolidation achieves long-term efficacy in primary acute promyelocytic leukemia.

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4% ± 3.9% and 94.6 ± 3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL.

Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPß contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPß could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPß. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPß in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.

Acute pleural and pericardial effusion induced by chemotherapy in treating chronic myelocytic leukemia.

BACKGROUND: Report of a rare and serious complication of chemotherapy with daunorubicin and cytarabine (DA regimen). METHODS: We report a special case of a patient diagnosed chronic myeloid leukemia (CML) with accelerated phase, who simultaneously suffered from acute pleural and pericardial effusion while receiving chemotherapeutic treatment with DA regimen. RESULTS: Following treatment with DA regimen, the patient had the symptoms of chest distress and shortness of breath, followed by respiratory failure and pericardial tamponade. The patient's condition was improved when treated with the puncturation through the pericardium and pleural cavity, coupled with glucocorticosteroid treatment. CONCLUSIONS: Physicians should be made aware of the potential for emergency pleural and pericardial effusion caused by daunorubicin and cytarabine in order to accurately diagnose and treat these conditions and thereby decrease mortality related to chemotherapy.

Diagnosis of Felty's syndrome, distinguished from hematological neoplasm: A case report.

Felty's syndrome (FS) is characterized by the three conditions of rheumatoid arthritis (RA), neutropenia and splenomegaly, and occurs in few cases of longstanding erosive RA. Discriminating between rare occurrences of autoimmune diseases and malignancies is crucial. The present study describes the case of a 17-year-old female with a two-year history of RA, presenting with an irregular fever, hepatosplenomegaly and enlarged lymph nodes. The antinuclear antibody titer was 1:320, while antibody results for anti-dsDNA, anti-Sm and rheumatoid factor were negative. The clinical presentation was similar to that of lymphoma. However, the fluorodeoxyglucose-positron emission tomography and biopsy examinations of the liver and cervical lymph node did not support the diagnosis of lymphoma. According to the laboratory results and clinical symptoms, the differential diagnosis indicated FS, and immunosuppressive agents were administered. Two weeks later, the patient no longer had a fever, and the transaminase levels were normal, associated with shrinkage of the liver and spleen.