Abstract
Acute myeloid leukemia (AML) is a malignant hematological disease in which nearly half have normal cytogenetics. We have tried to find some significant molecular markers for this part of the cytogenetic normal AML, which hopes to provide a benefit for the diagnosis, molecular typing and prognosis prediction of AML patients. In the present study, we calculated and compared the gene expression profiles of cytogenetically normal acute myeloid leukemia (CN-AML) patients in database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and dataset Vizome (a total of 632 CN-AML samples), and we have demonstrated a correlation between PDE7B gene and CN-AML. Then we proceeded to a survival analysis and prognostic risk analysis between the expression levels of PDE7B gene and CN-AML patients. The result showed that the event-free survival (EFS) and overall survival (OS) were significantly shorter in CN-AML patients with high PDE7B levels in each dataset. And we detected a significantly higher expression level of PDE7B in the leukemia stem cell (LSC) positive group. The Cox proportional hazards regression model showed that PDE7B is an independent risk predictor for CN-AML. All results indicate that PDE7B is an unfavorable prognostic factor for CN-AML.
Highlights
Acute myeloid leukemia (AML) is a group of malignant clonal hematological diseases that originate from hematopoietic stem cells (HSC) and is highly heterogeneous[1,2,3,4]
As the results presented in our research, we found that cytogenetically normal acute myeloid leukemia (CN-AML) patients with high expression of PDE7B had shorter survival times, suggesting that the PDE7B gene is an unfavorable prognostic marker for CN-AML
The results showed that the overall survival (OS) time of the low expression level of PDE7B group in the datasets GSE12417 U133B (162 patients, P < 0.0001, Log-rank test, Fig. 2A left), GSE71014 (104 patients, P < 0.0001, Log-rank test, Fig. 2A right), GSE22778 GPL8653 (54 patients, P < 0.0001, Log-rank test, Fig. 2B left) and GSE22778 GPL10107 (34 patients, P < 0.0001, Log-rank test, Fig. 2B right) was significantly longer
Summary
Acute myeloid leukemia (AML) is a group of malignant clonal hematological diseases that originate from hematopoietic stem cells (HSC) and is highly heterogeneous[1,2,3,4]. In 2001, the international hematology community launched the WHO diagnostic classification system for hematopoietic malignancies, namely the MICM (Morphological, Immunological, Cytogenetics, Molecular Biology) standard[6] This standard further systematically and comprehensively classified AML, which has important guiding significance for clinical treatment. Mutant genes obtained from 200 samples can be classified into a total of 9 categories according to biological function definitions, including transcription-factor fusions genes (The most statistically significant set, PML-RARA, MYH11-CBFB, RUNX1-RUNX1T1, PICALM-MLLT10, NUP98-NSD1, etc.), the gene encoding nucleophosmin (NPM1), tumor-suppressor genes (TP53, WT1, PHF6, etc.), DNA-methylation-related genes (DNMT3A, DNMT3B, DNMT1, TET1, TET2, IDH1, IDH2, etc.), signal transduction pathway-related genes (FLT3, KIT, KRAS, NRAS, PTPs, Ser-Thr kinase, etc.), chromatin-modifying genes (ASXL1, EZH2, KDM6A, MLL-related fusion genes, MLL-PTD, NUP98-NSD1, etc.), myeloid transcription-factor genes (RUNX1, CEBPA, etc.), cohesin-complex genes (STAG2, RAD21, etc.), and spliceosome-complex genes (SRSF2, SF3B1, ZRSR2, U2AF1, etc.) The discovery of these genes makes an important contribution to the accurate diagnosis of AML. As the results presented in our research, we found that CN-AML patients with high expression of PDE7B had shorter survival times, suggesting that the PDE7B gene is an unfavorable prognostic marker for CN-AML
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