Acute myeloid leukemia (AML) is a malignant tumor of the immature myeloid hematopoietic cells in the bone marrow (BM). It is a highly heterogeneous disease, with rising morbidity and mortality in older patients. Although researches over the past decades have improved our understanding of AML, its pathogenesis has not yet been fully elucidated. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are three noncoding RNA (ncRNA) molecules that regulate DNA transcription and translation. With the development of RNA-Seq technology, more and more ncRNAs that are closely related to AML leukemogenesis have been discovered. Numerous studies have found that these ncRNAs play an important role in leukemia cell proliferation, differentiation, and apoptosis. Some may potentially be used as prognostic biomarkers. In this systematic review, we briefly described the characteristics and molecular functions of three groups of ncRNAs, including lncRNAs, miRNAs, and circRNAs, and discussed their relationships with AML in detail.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the proliferation of immature myeloid cells, with impaired differentiation and maturation. Pyruvate dehydrogenase kinase (PDK) is a pyruvate dehydrogenase complex (PDC) phosphatase inhibitor that enhances cell glycolysis and facilitates tumor cell proliferation. Inhibition of its activity can induce apoptosis of tumor cells. Currently, little is known about the role of PDKs in AML. Therefore, we screened The Cancer Genome Atlas (TCGA) database for de novo AML patients with complete clinical information and PDK family expression data, and 84 patients were included for the study. These patients did not undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Univariate analysis showed that high expression of PDK2 was associated with shorter EFS (P = 0.047), and high expression of PDK3 was associated with shorter OS (P = 0.026). In multivariate analysis, high expression of PDK3 was an independent risk factor for EFS and OS (P < 0.05). In another TCGA cohort of AML patients who underwent allo-HSCT (n = 71), PDK expression was not associated with OS (all P > 0.05). Our results indicated that high expressions of PDK2 and PDK3, especially the latter, were poor prognostic factors of AML, and the effect could be overcome by allo-HSCT.

Acute myeloid leukemia (AML) is a malignancy caused by the uncontrolled and dysregulated clonal expansion of abnormal myeloid primordial cells. In general, the prognosis of AML remains poor despite new discoveries in its pathogenesis and treatment. It is crucial to find early and sensitive biomarkers and continue to explore active targeted treatments. Interferoninduced transmembrane protein (IFITM) family is an important part of the interferon signaling pathway and participate in the regulation of immune cell signaling, adhesion, cancer, and liver cell migration. However, the clinical and prognostic value of the IFITM family in AML has rarely been studied. We screened The Cancer Genome Atlas database and found 155 AML patients with IFITM family (IFITM1-5) expression data. In patients who only received chemotherapy, those with high IFITM3 expression had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expression (all P < 0.05). Multivariate analysis demonstrated that high IFITM3 expression was an independent risk factor for EFS and OS in patients only received chemotherapy (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, all IFITM members had no impact on either EFS or OS. In conclusion, our study elucidated that high IFITM3 expression could be an adverse prognostic factor for AML, whose effect might be overcome by allo-HSCT.

Microtubule-associated protein 7 (MAP7) plays an important role in cancer cells. In this study, we identified the prognostic significance of MAP7 expression in cytogenetically normal acute myeloid leukemia (CN-AML) patients (aged <60 years) based on several microarray datasets. In the first group (n = 129), high MAP7 expression (MAP7high) was associated with adverse overall survival (OS; P = 0.0441) and event-free survival (EFS; P = 0.0114) compared with low MAP7 expression (MAP7low). In addition, the prognostic significance of MAP7 was confirmed by European Leukemia Net (ELN) intermediate-I genetic categories and multivariable analysis. In the second independent group of CN-AML patients (aged <60 years), MAP7high was also associated with adverse OS (n = 88, OS; P = 0.00811). To understand the inherent mechanisms of MAP7’s prognosis, we investigated genome-wide gene/microRNA expression signatures associated with MAP7 expression. Several known oncogenic genes/microRNAs and anti-oncogenic genes/microRNAs were disordered in MAP7high CN-AML patients. In conclusion, MAP7high is an adverse prognostic biomarker for CN-AML, which may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.

MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 downregulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex. In this study, we demonstrate that miR-9-1 expression increases significantly after the treatment of RUNX1-RUNX1T1 (+) AML cell lines with decitabine (a DNMT inhibitor) and trichostatin A (an HDAC inhibitor). In addition, we show that RUNX1-RUNX1T1 triggers the heterochromatic silencing of miR-9-1 by binding to RUNX1-binding sites in the promoter region of miR-9-1 and recruiting chromatin-remodeling enzymes, DNMTs, and HDACs, contributing to hypermethylation of miR-9-1 in t (8; 21) AML. Furthermore, because RUNX1, RUNX1T1, and RUNX1-RUNX1T1 are all regulated by miR-9-1, the silencing of miR-9-1 enhances the oncogenic activity of these genes. Besides, overexpression of miR-9-1 induces differentiation and inhibits proliferation in t (8; 21) AML cell lines. In conclusion, our results indicate a feedback circuitry involving miR-9-1 and RUNX1-RUNX1T1, contributing to leukemogenesis in RUNX1-RUNX1T1 (+) AML cell lines.

iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study. Patients with high expressions of FHL2 and iASPP had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expressions (P = 0.005, P = 0.003, respectively). Univariate analysis indicated that high expressions of FHL2 or iASPP were unfavorable for EFS and OS (all P < 0.05), while multivariate analysis confirmed that high FHL2 expression was an independent risk factor for EFS and OS (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, EFS and OS were not significantly different between FHL2 or iASPP high- and low-expression groups. Our results suggested that high expressions of FHL2 and iASPP were poor prognostic factors for AML, but the prognostic effect might be overcome by allo-HSCT.

Background: Acute myeloid leukemia (AML) is a highly heterogenous hematological malignancy and its prognostication depends on the genetic mutation and expression profile of each patient. Pantothenate kinase (PANK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. It has four isoforms encoded by PANK1-4, respectively. Whether the expression of the PANK family has prognostic significance in AML remains unclear.Methods: We screened The Cancer Genome Atlas database for AML patients with complete PANK1-4 expression data. Eighty-four AML patients met the criteria and were included in this study. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations were described. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure.Results: Patients with high PANK2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than patients with low PANK2 expression (P=0.007, P=0.016, respectively), whereas patients with high PANK4 expression had shorter EFS and OS than patients with low PANK4 expression (P=0.022, P=0.015, respectively). Multivariate analysis confirmed that high PANK4 expression was an independent risk factor for EFS and OS (both P<0.05).Conclusions: Our study suggested that high PANK2 expression might have favorable effects on AML, while high PANK4 expression was indicative of poor prognosis.

Background : Actinins are major cytoskeletal proteins that mediate sarcomere function, and they also have important non-muscle functions such as regulating cytokinesis, cell adhesion and migration. There are four isoforms of actinins in mammals (ACTN1-4). Recently, the relationship between actinins and cancer has been discovered in many types of malignancy, yet their prognostic significance in acute myeloid leukemia (AML) remains unclear. Methods : We collected data of 155 de novo AML patients from The Cancer Genome Atlas (TCGA) database; 85 patients received chemotherapy only and 70 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We divided each treatment groups into sub-groups based on the median expression levels of ACTN1-4 . Results : Survival analysis showed that in the chemotherapy-only group, high ACTN1 and ACTN3 expression were associated with shorter event-free survival (EFS) and overall survival (OS) (p<0.01). Multivariate analysis suggested that high expression of ACTN1 and ACTN3 (p<0.05) were independent poor prognostic factors. In the allo-HSCT group, ACTN1-4 expression had no impact on survival. Conclusions : Our study suggested that high expression levels of ACTN1 and ACTN3 adversely affected the survival of AML patients, but their harmful impact could be overcome by allo-HSCT.