Enhanced expressions of FHL2 and iASPP predict poor prognosis in acute myeloid leukemia

Abstract

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.

Elevated Expression of Inhibitor of Apoptosis-stimulating Protein of p53 (iASPP) and Methyltransferase-like 3 (METTL3) Correlate with Poor Prognosis in FIGO Ib1-IIa Squamous Cell Cervical Cancer

“…Our results showed that elevated iASPP expression correlated with higher FIGO staging and more pelvic lymph node metastasis, and poor RFS, DMFS, PFS and OS. These data, consistent with previous studies [3][4][5][6][7][8][9][10], indicated that iASPP, as a newly identified oncoprotein, was involved in the carcinogenesis and progression of early stage cervical cancer and might serve as novel potential therapeutic target. Dong et al [4] demonstrated that miR-124, directly targeting iASPP, reduces expression of iASPP and attenuated cervical cancer cell growth and invasiveness.…”

“…iASPP plays an important role in regulating p53 dependent apoptosis and acts as a negative regulator of the tumor suppressor p53 [19]. iASPP overexpression was discovered in tumor tissues and moreover associated to poor prognosis and survival in some types of cancers [5][6][7][8][9]. Targeted suppression of iASPP may serve as the mechanism by which its upstream protein prevents oncogenesis of cancer [19,20].…”

“…iASPP acts as a key promoter of cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness by interacting with p53 to suppress p53-mediated transcription of target genes [3,4]. iASPP is overexpressed in many human cancers, including cervical cancer, leukemia, ovarian clear cell carcinoma, hepatocellular carcinoma, and non-small cell lung cancer [5][6][7][8][9]. The increased expression of iASPP confers proliferative, migratory, and invasive capacities to cancer cells, and is associated with advanced stage, lymph node metastasis, chemoresistance, radioresistance and decreased survival [10].…”

Up‐regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia

“…In addition to genetic mutations, aberrant oncogene expressions have also been proposed as a tool for risk stratification. For example, high expressions of sFRP2 and DOK7 may suggest better prognosis, but high expressions of FHL2 and iASPP may indicate poor survival in AML …”

Upregulation of Glutamic-Oxaloacetic Transaminase 1 Predicts Poor Prognosis in Acute Myeloid Leukemia

“…Additionally, abnormal oncogene expressions have attracted more attention in recent years, with great potentials to be incorporated into a refined AML risk stratification system (3,4). For example, high expressions of the secreted frizzled-related protein 2 (sFRP2) and docking protein 7 (DOK7) genes are associated with better outcome (5,6), while high expressions of FHL2 and iASPP are associated with poor survival in AML (7).…”