MiR-181a-2-3p as a potential diagnostic and prognostic marker for myelodysplastic syndrome.

OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder with a high propensity to develop into acute myeloid leukemia (AML). Although abnormal microRNA expression has been implicated in MDS, the exact role of miR-181a-2-3p has not been entirely elucidated. Here, we investigated miR-181a-2-3p levels in bone marrow (BM), and described its utility as a potential indicator for MDS diagnosis and prognosis. METHODS: We evaluated miR-181a-2-3p expression in BM samples of 54 newly diagnosed MDS cases, 16 sAML patients and 32 healthy donors and then assessed its association with clinical characteristics and its potential value for MDS diagnosis and prognosis. RESULTS: Compared with healthy controls, miR-181a-2-3p levels were decreased in the total cohort of MDS patients. Additionally, in MDS patients with secondary AML (sAML), miR-181a-2-3p was over-expressed relative to levels in those without this form. The areas under the curve of receiver operating characteristic curves were 0.700 and 0.750 to distinguish MDS patients from controls and sAML from newly diagnosed MDS, respectively. Kaplan-Meier analysis showed a positive correlation between miR-181a-2-3p expression and overall survival (OS). Further, multivariate analysis indicated that miR-181a-2-3p was an independent prognostic index for MDS with respect to OS. CONCLUSION: Decreased miR-181a-2-3p expression in MDS patients may be considered as one of the underlying markers reflecting MDS progression and prognosis.

Landscape of T Cells in NK-AML(M4/M5) Revealed by Single-Cell Sequencing.

Normal karyotype acute myeloid leukemia (NK-AML) is a highly heterogeneous malignancy that resides within a complex immune microenvironment, complicating efforts to reveal the interaction between leukemia cells and immune cells. Understanding tumor-infiltrating T cells is crucial to the advancement of immune therapies and the improvement of the prognosis for NK-AML patients. We performed single-cell RNA sequencing on bone marrow cells from 5 NK-AML (M4/M5) patients and 1 normal donor and paired single-cell T cell receptor (TCR) sequencing on single T cells. As a result, we identified 8 T cell clusters based on the gene expression characteristics of each subset in NK-AML and described their developmental trajectories. In NK-AML patients, specific clusters, such as mucosal-associated invariant T cells (MAITs), were preferentially enriched and potentially clonally expanded. These transcriptome and TCR data analyses provide valuable insights and rich resources for understanding the immune environment of NK-AML.

Clinical Significance of Decreased GPX1 Expression in Patients with Acute Myeloid Leukaemia (Non-M3).

OBJECTIVE: To determine the expression levels of GPX1, SOCS5 and IL7 and their clinical significance in patients with acute myeloid leukaemia (AML). STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China, from January 2013 to November 2020. METHODOLOGY: Based on the bioinformatics analysis, the expression levels of GPX1, SOCS5 and IL7 in the bone marrow of 64 AML patients (non-M3) and 32 healthy individuals were evaluated by real-time PCR. Correlation between GPX1 expression and the clinical characteristics, response to induced chemotherapy, and survival time of AML patients were analysed as the outcome measure. RESULTS: GPX1 was significantly downregulated in AML patients, which helped in distinguishing AML patients from normal controls. The area under the curve (AUC) of the receiver operator characteristic (ROC) was 0.741 (p <0.001). Additionally, GPX1 expression was correlated with gender (r = -0.250, p = 0.045), FAB classification (r = -0.332,  p = 0.004), and chemotherapy response (r = 0.366, p = 0.003). AML patients with high GPX1 expression levels had a lower rate of remission (p = 0.021) and poor long-term survival (p = 0.036) than those with low GPX1 expression levels. CONCLUSION: Low GPX1 expression in AML patients may be closely associated with the pathogenesis and chemoresistance of AML. Key Words: Acute myeloid leukaemia, Clinical outcome, Gene expression, GPX1.

Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P < 0.0001), 0.7515 (P = 0.0002), 0.9647 (P < 0.0001), 0.8064 (P < 0.0001) and 0.9019 (P < 0.0001). Regarding Kaplan-Meier analysis, high miR-320c and miR-320d expression were related to shorter overall survival (OS). Moreover, multivariate analysis revealed the independent prognostic value of miR-320d for OS in MDS. The expression of miR-320 family members was up-regulated in MDS, and miR-320 family members could serve as candidate diagnostic biomarkers for MDS. High expression of miR-320d was an independent prognostic factor for OS in MDS.

Identification the prognostic value of glutathione peroxidases expression levels in acute myeloid leukemia.

BACKGROUND: Glutathione peroxidases (GPXs) are an enzyme family with peroxidase activity. Abnormal GPX expression is associated with carcinogenesis. However, the potential role of the GPX gene family in acute myeloid leukemia (AML) remains to be comprehensively examined. METHODS: We analyzed GPX mRNA expression levels and determined the correlation between gene expression and the prognostic value via multiple universally acknowledged databases including the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), PROGgeneV2, UALCAN, Cancer Cell Line Encyclopedia (CCLE), and The European Bioinformatics Institute (EMBL-EBI) databases. The functional network of differentially expressed GPXs was investigated via the NetworkAnalyst platform. Correlated genes as well as kinase, microRNA (miRNA), and transcription factor (TF) targets were identified using LinkedOmics. RESULTS: We observed that the transcriptional expression levels of GPX-1, -2, -4, -7, and -8 had significant difference between AML patients samples and normal samples, and that AML patients with high expression of GPX-1, -3, -4, and -7 were associated with poorer prognosis of overall survival (OS). Functional enrichment analysis showed that the differentially expressed GPXs were mainly enriched in response to oxidative stress, regulation of immune response, and inflammatory response, along with glutathione metabolism and ferroptosis. Overexpression of correlated genes, PSMB10, VPS13D, NDUFS8, ATP5D, POLR2E, and HADH were linked to adverse OS in AML. Regulatory network analysis indicated that differentially expressed GPXs regulated cell proliferation, cancer progression, apoptosis, and cell cycle signaling via pathways involving cancer-related kinases (such as DAPK1 and SRC), miRNAs (such as miR-202 and miR-181), and TFs (such as SRF and E2F1). CONCLUSIONS: Our findings offer novel insights into the differential expression and prognostic potential of the GPX family in AML, and lay a foundation for subsequent research of GPX's role in the carcinogenesis and regulatory network of AML.

Microarray analysis of differentially expressed microRNAs in myelodysplastic syndromes.

BACKGROUND: Our study aimed to analyze differential microRNA expression between myelodysplastic syndromes (MDS) and normal bone marrow, and to identify novel microRNAs relevant to MDS pathogenesis. METHODS: MiRNA microarray analysis was used to profile microRNA expression levels in MDS and normal bone marrow. Quantitative real-time polymerase chain reaction was employed to verify differentially expressed microRNAs. RESULTS: MiRNA microarray analysis showed 96 significantly upregulated (eg, miR-146a-5p, miR-151a-3p, miR-125b-5p) and 198 significantly downregulated (eg, miR-181a-2-3p, miR-124-3p, miR-550a-3p) microRNAs in MDS compared with normal bone marrow. The quantitative real-time polymerase chain reaction confirmed the microarray analysis: expression of six microRNAs (miR-155-5p, miR-146a-5p, miR-151a-3p, miR-221-3p, miR-125b-5p, and miR-10a-5p) was significantly higher in MDS, while 3 microRNAs (miR-181a-2-3p, miR-124-3p, and miR-550a-3p) were significantly downregulated in MDS. Bioinformatics analysis demonstrated that differentially expressed microRNAs might participate in MDS pathogenesis by regulating hematopoiesis, leukocyte migration, leukocyte apoptotic process, and hematopoietic cell lineage. CONCLUSIONS: Our study indicates that differentially expressed microRNAs might play a key role in MDS pathogenesis by regulating potential relevant functional and signaling pathways. Targeting these microRNAs may provide new treatment modalities for MDS.

Expression and Clinical Significance of ANXA1 and DICER1 in Myelodysplastic Syndromes.

OBJECTIVE: To explore the expression status of ANXA1 and DICER1 and their clinical significance in myelodysplastic syndromes (MDS) patients.  Study Design: A case control study. PLACE AND DURATION OF STUDY: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China, from January 2011 to June 2020. METHODOLOGY: Quantitative real-time fluorescence PCR (qRT-PCR) was carried out to detect ANXA1 and DICER1 expression levels in the bone marrow from 49 MDS patients and 12 healthy volunteers as control. The correlation of the clinical parameters and ANXA1 or DICER1 expression was then analysed in MDS. RESULTS: Compared with normal controls, the expression of bone marrow ANXA1 and DICER1 in MDS patients was significantly decreased, especially in patients with secondary acute myeloid leukemia (s-AML). Moreover, down-expression of ANXA1 had a great effect on differentiating s-AML subjects from MDS cases, and DICER1 expression showed good performance to screen MDS subjects from normal controls. ANXA1 expression was negatively correlated with clinical features of poor prognosis such as the percentage of bone marrow blasts, IPSS and WHO subtypes. CONCLUSIONS:  Bone marrow ANXA1 may be a potential biomarker for the risk prediction of leukemia transformation in MDS. DICER1 may have diagnostic significance to MDS. Key Words: Myelodysplastic syndrome, Secondary acute myeloid leukemia, ANXA1, DICER1.

Rhabdomyolysis during myelosuppression in a patient with central nervous system leukemia: A case report.

RATIONALE: Rhabdomyolysis is a potentially life-threatening syndrome and is a rare complication in patients with acute leukemia. PATIENT'S CONCERNS: A 20-year-old male was admitted to our hospital due to skin ecchymosis in his trunk and lower limbs for 10 days. DIAGNOSES: Based on the precise diagnosis of leukemia, namely cell morphology, immunology, cytogenetics, and molecular biological typing (MICM), the patient was diagnosed with acute T-lymphocytic leukemia (T-ALL). INTERVENTIONS: The patient received hyper-Cyclophosphamide, Vincristine,Adriamycin, Dexamethasone (hyper-CVAD) regimen chemotherapy (methotrexate, pirarubicin, vincristine and dexamethasone alternating with methotrexate and cytarabine) for 3 courses of chemotherapy. After 3 months of treatment, the patient developed intermittent pain, blurred vision, and inarticulate speech. Therefore, the patient was considered as central nervous system leukemia (CNSL) and immediately received 2 courses of chemotherapy with hyper-CVAD-B combined with polyethylene glycol conjugated asparaginase (PEG-ASP). OUTCOMES: On the seventh day after the completion of chemotherapy, the patient was diagnosed with rhabdomyolysis because he complained of perianal pain and hematuria, and his creatine kinase (CK) increased suddenly to 3136 U/L. Finally, the patient died despite all kinds of active rescue. LESSONS: Rhabdomyolysis may occur after chemotherapy of leukemia. When patients developed hematuria, muscle weakness, or even asymptomatic elevation of CK levels, physicians should pay attention to the occurrence of rhabdomyolysis and take active hydration treatment.