scholarly journals High expression of dedicator of cytokinesis 1 (DOCK1) confers poor prognosis in acute myeloid leukemia

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 72250-72259 ◽  
Author(s):  
Sze-Hwei Lee ◽  
Yu-Chiao Chiu ◽  
Yi-Hung Li ◽  
Chien-Chin Lin ◽  
Hsin-An Hou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
High Expression ◽  
Acute Myeloid

scholarly journals High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemia

1998 ◽  
Vol 9 (2) ◽  
pp. 159-165 ◽  
Author(s):  
T. Karakas ◽  
U. Maurer ◽  
E. Weidmann ◽  
C.C. Miething ◽  
D. Hoelzer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
High Expression ◽  
Acute Myeloid

High expression of miR‐338 is associated with poor prognosis in acute myeloid leukemia undergoing chemotherapy

2019 ◽  
Vol 234 (11) ◽  
pp. 20704-20712 ◽  
Author(s):  
Lin Fu ◽  
Jialei Qi ◽  
Xiang Gao ◽  
Ninghan Zhang ◽  
Huihui Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
High Expression ◽  
Acute Myeloid

High expression of SLC38A1 predicts poor prognosis in patients with de novo acute myeloid leukemia

2019 ◽  
Vol 234 (11) ◽  
pp. 20322-20328 ◽  
Author(s):  
Yan Li ◽  
Haigang Shao ◽  
Zhenzhen Da ◽  
Jinlan Pan ◽  
Bin Fu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
De Novo ◽  
High Expression ◽  
Acute Myeloid

High expression of HOXA5 is associated with poor prognosis in acute myeloid leukemia

2020 ◽  
pp. 100673
Author(s):  
You Yang ◽  
Fangfang Zhong ◽  
Xiaoming Huang ◽  
Na Zhang ◽  
Jingjing Du ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
High Expression ◽  
Acute Myeloid

scholarly journals High Expression of BCAT1 promotes Acute Myeloid Leukemia Progression and Sensitize to PARP Inhibitor

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5041-5041
Author(s):  
Jie Jin ◽  
Jie Jin ◽  
Jiajia Pan ◽  
Yungui Wang ◽  
Shujuan Huang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Parp Inhibitor ◽  
High Expression ◽  
Parp Inhibition ◽  
Branched Chain ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous disease with poor clinical prognosis, especially to cytogenetically normal AML(CN-AML)patients, which belong to moderate prognosis group. The clinical outcomes of them are not consistent. Therefore, further exploration of novel biomarkers and development of new anti-tumor drugs is urgently needed. Recently, accumulating evidence have emerged and demonstrated that branched-chain amino acids (BCAA) are essential for tumor growth and proliferation. Branched-chain aminotransferase 1(BCAT1), a BCAA metabolic enzyme, which correlates with cancer aggression, not only that, it has been reported that overexpression of BCAT1in leukemia cells decreased intracellular αKG levels, showed the characteristics of stem cells and displayed a phenotype like cases carrying IDH mutations. By limiting intracellular αKG, BCAT1high expression AML cells prone to cause an increase in DNA damage probably via suppressing homologous recombination. We firstly analyzed the prognostic significance of BCAT1expression in CN-AML patients. Collectively, we found that patients with high levels of BCAT1had poor prognosis, the median overall survival time is shorter in BCAT1high group (356 days versus 570 days)(Figure A). Next, we performed gene knockout in THP-1 and MV4-11 cells with relatively high expression of BCAT1and gene overexpressing in the relatively low expression cell line OCI-AML3. In summary, BCAT1overexpression contributed to cell growth, whereas suppression of BCAT1markedly limited cell proliferation and colony-forming ability by blocking cell circle at G0/G1 phase(Figure B and C).The mice model we conducted further validated the role of BCAT1expression in vitro. Notably, we found that knockout and overexpression of BCAT1can respectively reduce and enhance the tumor burden(Figure D)and effects the time of survival(Figure E). Because both BCAT1high expression and IDH mutation could decrease αKG levels and suppress αKG dependent dioxygenases, it is tempting to speculate that there is a possibility of a "BRCAness" phenotype when BCAT1is overexpressed.We indeed observed a rise in the base line level of DNA damage marker γ-H2AX in BCAT1overexpressing cell line(Figure F). In addition, the sensitivity of cells to cisplatin is also positively correlated with BCAT1expression levels, the IC50 of BCAT1overexpressing cell line OCI-AML3 is much lower than control. Consistently, knocking out of BCAT1decreased sensitivity to cisplatin. So we further tested the relationship between PARPi talazoparib(BMN 673) and BCAT1expression, Use a gain of function approach we increased susceptibility to PARPi, together with the loss of function data, these results strongly suggest that BCAT1promotes cell sensitivity to PARPi(Figure G). We believe that the combination of high expression of BCAT1and PARPi produces synthetic lethality. In addition, the ability to trap PARP1 of PARPi may produce unacceptable toxicity when combined with conventional doses of cytotoxic chemotherapies. So, we next combined PARP inhibitors with DNA-damaging agent daunorubicin, the synergistic effect is promising on BCAT1overexpressed OCI-AML3 cell especially at high dose, however, the synergistic effect of the control group is weak, sometimes even manifested as antagonistic.Consistent with previous reports, IDH1/2mutAML is vulnerable to PARP inhibition as monotherapy, but especially when combined with daunorubicin treatment. These results also confirmed our hypothesis that BCAT1overexpression mimics the phenotype of IDHmutcells, not only as DNA hypermethylation, but also leads to increased DNA damage levels in cells, increasing sensitivity to PARP inhibitor and DNA-damaging drugs. Through qPCR and WB assays, we found the same trend: DNA damage response-related protein ATM was down-regulated after BCAT1overexpression, which preliminarily explained why DNA damage was increased after BCAT1overexpression. After exogenous supplementation with the aKG analog DM-aKG, the enhancement of DNA damage caused by overexpression of BCAT1can be reversed. In summary, this study indicated that CN-AML patients with high BCAT1expression had poor prognosis. BCAT1plays the role as oncogene, can induce DNA damage that renders AML cells sensitive to PARP inhibition and DNA damage agents, and can be used as a novel therapeutic option for AML. Figure Disclosures No relevant conflicts of interest to declare.

High expression of ISG20 predicts a poor prognosis in acute myeloid leukemia

2021 ◽  
pp. 1-7
Author(s):  
Hao Xiong ◽  
Xinwen Zhang ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
Jialin Duan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cox Regression ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Receive Treatment ◽  
To Receive ◽  
Acute Myeloid

BACKGROUND: Acute myeloid leukemia (AML) is one of the most malignant hematopoietic system diseases. Interferon stimulated exonuclease gene 20 (ISG20) is a protein induced by interferons or double-stranded RNA, which is associated with poor prognosis in several malignant tumors. However its expression in AML is unknown. OBJECTIVE: To explore the expression of ISG20 in AML and its prognostic significance. METHODS: The expression of ISG20 in AML patients was analyzed by GEPIA database, detected by qRT-PCR and their prognosis was followed-up. Chi-square test was used to identify the association between ISG20 expression and clinical characteristics of the patients. Kaplan-Meier analysis was performed to draw survival curves and Cox regression analysis to confirm the independent prognostic factors of AML patients. RESULTS: Kaplan-Meier analysis revealed that whether to receive treatment, Karyotype, and ISG20 expression were related to overall survival time of AML patients (P< 0.05). Cox regression analysis showed that whether to receive treatment (HR = 0.248, 95% CI = 0.076–0.808, P= 0.021) and high expression of ISG20 (HR = 4.266, 95% CI = 1.118–16.285, P= 0.034) were independent unfavorable prognostic factors for AML patients. CONCLUSION: The high expression of ISG20 acts as a poor prognosis indicator in AML patients.

scholarly journals High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia

2021 ◽  
Vol 20 ◽  
pp. 153303382110658
Author(s):  
Dan Mu ◽  
Sili Long ◽  
Ling Guo ◽  
Wenjun Liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Western Blotting ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
High Expression ◽  
Control Group ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Acute Myeloid

Objectives: VAV family genes ( VAV1, VAV2, and VAV3) are associated with prognosis in various cancers; however, they have not been evaluated in acute myeloid leukemia (AML). In this study, the prognostic value of VAV expression in AML was evaluated by a single-center study in combination with bioinformatics analyses. Methods: The expression and prognostic value of VAVs in patients with AML were investigated using various databases, including GEPIA, CCLE, EMBL-EBI, UALCAN, cBioPortal, STRING, and DAVID. Blood samples from 35 patients with AML (non-M3 subtype) and 13 benigh individuals were collected at our center. VAV expression levels were detected by real-time quantitative PCR (RT-qPCR) and western blotting. Clinical data were derived from medical records. Results: Based on data from multiple databases, the expression levels of VAV1, VAV2, and VAV3 were significantly higher in AML than in control tissues ( P < 0.05). RT-qPCR and western blotting results showed that VAV expression in mRNA and protein levels were higher in patients with AML that in the control group ( P < 0.05). Complete remission rates were lower and risks were higher in patients with AML with high VAV1 expression than with low VAV1 expression ( P < 0.05). High levels of VAV2, VAV3, and VAV1 were related to a poor overall survival, and this relationship was significant for VAV1 ( P < 0.05). High expression levels of genes correlated with VAV1, such as SIPA1, SH2D3C, and HMHA1 were also related to a poor prognosis in AML. Functional and pathways enrichment analyses indicated that the contribution of the VAV family to AML may be mediated by the NF-κB, cAMP, and other pathways. Conclusion: VAVs were highly expressed in AML. In particular, VAV1 has prognostic value and is a promising therapeutic target for AML.

High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy

2018 ◽  
Vol 26 (5-6) ◽  
pp. 119-127 ◽  
Author(s):  
Jilei Zhang ◽  
Lingxiu Zhang ◽  
Haoran Cui ◽  
Xinpei Zhang ◽  
Gaoqi Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
High Expression ◽  
Expression Levels ◽  
Acute Myeloid
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