Identification of Novel Molecular Markers for Prognosis Estimation of Acute Myeloid Leukemia: Over-Expression of PDCD7, FIS1 and Ang2 May Indicate Poor Prognosis in Pretreatment Patients with Acute Myeloid Leukemia

Abstract

Numerous factors impact on the prognosis of acute myeloid leukemia (AML), among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML) patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029). In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035). Overall survival (OS) and relapse-free survival (RFS) were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006), and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004). In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039). As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML.

Exacerbation of mitochondrial fission in human CD34+cells halts erythropoiesis and hemoglobin biosynthesis

“…Furthermore, our results supports the evidence of excessive levels of FIS 1 as a molecular marker of myeloid leukemia 45 .…”

“…Excessive mitochondrial fission has been associated with a decreased mitochondrial function and increased ROS 41,42 . FIS1 up-regulation decreased cellular ATP levels in anoxic cardiomyocytes and impaired glucose-stimulated insulin secretion in INS-1E cells 43,44 ; and it has been identified as a molecular marker for poor prognosis in patients with acute myeloid leukemia 45 . We observed that erythroid differentiation under FIS1 overexpression was arrested mainly at the proerythroblast level with mitochondria featuring reduced complex II and IV protein expression and membrane potential; and an immature phenotype i.e.…”

Polymerase Acidic Subunit of H9N2 Polymerase Complex Induces Cell Apoptosis by Binding to PDCD 7 in A549 Cells

“…Mouse PDCD7 was rst identi ed using the screening approach in 1999 and characterized as an apoptosis-related protein that involves in apoptotic cell death of T-cells [29]. However, the speci c function of PDCD7 in human is still unknown, although several studies have reported that human PDCD7 may related to the acute myeloid leukemia (AML) [30,31]. Compared with the non-malignant samples, higher PDCD7 expression was found in AML patients and related to lower complete remission rate, shorter relapse-free survival, and overall survival, suggesting that overexpression of PDCD7 may serve as a molecular marker for prognosis estimation of AML [30,31].…”

The Mitochondrial Genes BAK1, FIS1 and SFN are Linked with Alterations in Mitochondrial Membrane Potential in Barrett’s Esophagus

“…We have shown that, FIS1 , known to play important roles in apoptosis and mitochondrial fission, was shown to significantly increase across the disease sequence and this change was only seen in the Barrett’s tissue compared to matched surrounding mucosa. FIS1 is a novel gene target associated with poor prognosis in pre-treatment patients with acute myeloid leukemia [ 24 ]. Conversely, it is also upregulated in patients with non-metastatic prostate cancer [ 25 ] and plays a role in cisplatin resistance in tongue squamous cell carcinoma with cisplatin sensitivity being restored upon knockdown of FIS1 [ 26 ].…”