Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

An adolescent with primary cutaneous follicle center lymphoma: a case report and literature review.

Primary cutaneous follicle center lymphoma (PCFCL) differs from follicular lymphoma in biological behavior and molecular profile and is treated as a distinct entity, according to the 5th edition of the World Health Organization classification of hematolymphoid tumors. It is an uncommon cutaneous B-cell lymphoma that is considerably rare in children and adolescents. To date, only 13 cases of individuals younger than 20 years of age have been reported in the literature. The lack of relevant clinical epidemiological data in this population has hampered the investigation of its clinical and diagnostic aspects. Here we report the case of a 17-year-old male with PCFCL, who may be the first PCFCL patient under 20 years of age reported in China. He was admitted to the hospital with a solitary nodule on his face. After complete surgical excision, the patient's facial mass was histologically identified as PCFCL. The patient's prognosis was favorable, with no recurrence at 17 months of follow-up after the surgical resection. We present a case of an adolescent PCFCL patient and systematically review the literature with a view to increase the awareness of the disease and inform the diagnosis and treatment of this age group.

Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report.

Waldenström macroglobulinemia (WM) rarely leads to pulmonary embolism. Due to its low incidence, the underlying pathophysiology, prognosis, and optimal treatment remain largely unexplored and uninvestigated. In this study, a patient with a double-clonal WM, a rare subtype, presented with pulmonary embolism. The patient had a small number of plasma cells without morphological abnormalities, and an effective therapeutic response was observed. Nonetheless, the clinical prognosis requires a long-term follow-up.

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.

[High Risk Factors for Transformation into Acute myeloid Leukemia in Patients with Intermediate and High Risk Myelodysplastic syndrome].

OBJECTIVE: To study the high risk factors for the transformation into acute myeloid leukemia(AML) in patients with intermediate and high risk myelodysplastic syndrome(MDS) treated by decitabine-based regimen. METHODS: The clinical characterstics of 60 intermediate and high risk MDS patients and the factors of its transformed into AML were retrospectively analyzed. RESULTS: The overall response rate(ORR) of the patients suffered from intermediate and high risk MDS treated by decitabine-based regimen was 65.0％(39/60), among the 60 cases 17 achieved complete remission(CR), 5 achieved morrow complete remission(mCR), 4 achieved partial remission(PR) and 13 achieved hematologic improvement(HI). Twenty-one cases(35.0%) were transformed into AML among 60 cases of intermediate and high risk MDS treated by decitabine-based regimen. The median time of transformation from intermediate and high risk MDS into AML was 10.0 months(1.6-32.0). χ2 or Fisher's exact test showed that 2016 WHO MDS diagnostic subgrouping, myeloid hyperplasia markedly active, delayed interval of decitabine-based treatment associated with the transformation from intermediate to high risk MDS into AML (χ2=9.878，P=0.031；χ2=4.319，P=0.038；χ2=6406，P=0.011); Univariate analysis of Kaplan-Meier test showed that 2016 WHO MDS diagnostic subgroups, bone marrow blast cell ratio, bone marrow dysplasia coefficients, prolonged interval of decitabine-based treatment associated with the transformation from intermediate and high risk MDS into AML (P=0.015，P=0.008，P=0.012，P=0.032); multivariate analysis showed the bone marrow blast cell ratio and the bone marrow dysplasia coefficients were independent risk factors for the transformation from intermediate to high risk MDS into AML (P=0.022，P=0.018). CONCLUSION: The bone marrow blast cell ratio and the bone marrow dysplasia coefficients are independent risk factors of transformation into AML in the patients with intermediate and high risk MDS treated by decitabine-based regimen. The regular interval of dicitabine treatment is beneficial to maintain the stability of patients conditions.

The Effect of Ras Homolog C/Rho-Associated Coiled-Protein Kinase (Rho/ROCK) Signaling Pathways on Proliferation and Apoptosis of Human Myeloma Cells.

BACKGROUND The aim of this study was to explore the impact of Ras homolog C/Rho-associated coiled-protein kinase (Rho/ROCK) signaling pathways intervention on biological characteristics of the human multiple myeloma cell lines RPMI-8226 and U266 cells, and to investigate the expression of RhoC, ROCK1, and ROCK2 in RPMI-8226 and U266 cells. MATERIAL AND METHODS RPMI8226 and U266 cell lines were treated by 5-aza-2-deoxycytidine (5-Aza-Dc), trichostatin A (TSA), RhoA inhibitor CCG-1423, Rac1 inhibitor NSC23766, and ROCK inhibitor fasudil. Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and clone formation. Cell apoptosis was examined by flow cytometry and TUNEL assay. The mRNA and protein expressions of RhoC, ROCK1, and ROCK2 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot, respectively. RESULTS CCG-1423, NSC23766, and fasudil could significantly inhibit the proliferation of RPMI8226 and U266 cells. The inhibitory effect was dose- and time-dependent within a certain concentration range (P<0.05). After treatment with CCG-1423, NSC23766, and fasudil for 24 hours, the apoptosis rates of RPMI8226 and U266 cells were significantly higher than those of the control group, which were dose-dependent (P<0.05). Compared with the control group, the mRNA and protein expressions of RhoC, ROCK1, and ROCK2 in RPMI8226 and U266 cells were significantly decreased with single 5-Aza-Dc or TSA treatment. However, the effects were obviously stronger after combined treatment of 5-Aza-CdR and TSA (P<0.05). CONCLUSIONS We found that 5-Aza-Dc and TSA can effectively decrease the mRNA and protein expressions of RhoC, ROCK1, and ROCK2. Furthermore, Rho and ROCK inhibitors significantly inhibit cell growth and induce cell apoptosis in the human multiple myeloma cell lines RPMI-8226 and U266.

Decitabine: An effective and safe treatment for myelodysplastic syndrome and acute myeloid leukemia.

OBJECTIVE: Decitabine is reported to be valuable in treating multiple malignant blood diseases. However, the application of decitabine in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) has not been fully examined. Thus, our study aimed to investigate the clinical efficacy and safety of decitabine in treating such patients. MATERIALS AND METHODS: Clinical data of MDS or AML patients treated with decitabine were retrospectively analyzed. All the patients were regularly followed up, and the risk factors affecting clinical efficacy were also detected. RESULTS: A total of 36 patients (MDS, n = 27; AML, n = 9) were included in the study. The response rate of MDS patients was 55%, and there were three cases (15%) of complete remission (CR), three cases (15%) of marrow CR, and five cases (15%) of hematologic improvement. It was about three cycles to achieve the best efficiencies. Gender, age, percentage of blasts in bone marrow, International Prognostic Scoring System risk group, and cytogenetic factors were not associated with response rate. The median overall survival of MDS patients was 8 (1-44) months. Agranulocytosis (P = 0.037) and severe anemia (P = 0.044) were the independent factors for prognosis. The complete response rate of AML was 33.3%. From the investigation, infection was the most common complication in our cohort, especially lung infection with the incidence of 27.8%. CONCLUSIONS: Our data demonstrated that decitabine was effective and relatively safe in treating MDS and AML. Patients with agranulocytosis and severe anemia were prone to have poor survival, which should be monitored in clinical practice.