scholarly journals Risk Stratification in Acute Myeloid Leukemia Using CXCR Gene Signatures: A Bioinformatics Analysis

2020 ◽  
Vol 10 ◽  
Author(s):  
Cong Lu ◽  
Jiang Zhu ◽  
Xiangjun Chen ◽  
Yanjie Hu ◽  
Wei Xie ◽  
...  

The role of CXC chemokine receptors in tumors has been an increasingly researched focus in recent years. However, significant prognostic values of CXCR members in acute myeloid leukemia are yet to be explored profoundly. In this study, we firstly made an analysis of the relationship of CXCR family members and AML using samples from TCGA. Our results suggested that transcriptional expressions of CXCRs serve an important role in AML. CXCR transcript expressions, except CXCR1 expression, were significantly increased in AML. It displayed the expression pattern of CXCR members in different AML subtypes according to FAB classification. The correlations of CXCR transcript expression with different genotypes and karyotypes were also present. High CXCR2 expression was found to have a significantly worse prognosis compared with that of low CXCR2 expression, and CXCR2 was also found to be an independent prognostic factor. We also established a CXCR signature to identify high-risk subgroups of patients with AML. It was an independent prognostic factor and could become a powerful method to predict the survival rate of patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18516-e18516
Author(s):  
Heba A. Ahmed ◽  
Ahmed M. Maklad ◽  
Ashraf Elyamany

e18516 Background: Acute myeloid leukemia (AML) is one of the most common leukemia affecting adult. Regulatory T cells (Tregs) are a subset of CD4 (+) T cells that plays a central role immune tolerance. Objective: We aimed to explore the role of interleukin- 27 (IL27) & interleukin- 35 (IL35) produced by T regs and its associations with clinical characteristics and prognostic markers of AML patients. Methods: The study included 70 patients with acute myeloid leukemia (AML) and 30 healthy controls. We used flowcytometry immunophenotyping to confirm the diagnosis of AML. Serum level of interleukin- 27 (IL 27) & interleukin- 35 (IL 35) were measured at diagnosis by enzyme-linked immunosorbentassay (ELISA). Results: Higher levels of IL27 and IL35 were detected in AML patients than the control group (p ≤ 0.001). We used Receiver operating characteristic (ROC) analysis for detection of optimum IL27 & IL35 cut off level needed for predicting AML. ROC curve analysis demonstrated IL27 optimum cutoff is > 43, AUC 0.926 with a sensitivity 74% and Specificity 96.6% (P-value <0.00). IL35 optimum cutoff was > 27.8 AUC 0.972 with 88% and 98% sensitivity and specificity respectively (P-value <0.001). Serum IL27 & IL35 could well identify AML patients from healthy individuals. More importantly IL27 & IL35 correlated with clinical variable, and could be served as an independent prognostic factor. Conclusions: IL27 & IL 35 might have an application as a diagnostic and prognostic indicator for AML patients and could be served as an independent prognostic factor.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Li ◽  
Zheng Ge

Abstract Background Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA). Conclusions Our research revealed HSPA8 as a novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with the HSPA8 high expression in AML.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1802-1802
Author(s):  
Brian V Balgobind ◽  
Sanne Lugthart ◽  
Iris H.I.M. Hollink ◽  
Susan T.J.C.M. Arentsen-Peters ◽  
Elisabeth R van Wering ◽  
...  

Abstract The EVI1 (ecotropic virus integration-1) gene plays an important role in hematopoiesis especially in megakaryocyte development. The MDS1 gene is located upstream of EVI1, and its function is currently unknown. Normally the MDS1/EVI1 intergenic splice variant is co-expressed with EVI1. In adult acute myeloid leukemia (AML) overexpression of EVI1 (EVI1+) can be found in patients with chromosome 3q26-rearrangements. Often, these patients do not co-express MDS1/EVI1. Recently high EVI1 expression was also discovered in a separate subgroup of patients that did not have 3q26-rearrangements. Occasionally, they did not show overexpression of MDS1/EVI1. In these patients cryptic inversions of chromosome 3 were identified with fluorescence in situ hybridization (FISH). Of interest, EVI1+ was found to be an independent poor prognostic marker in adult AML (Lugthart et al, Blood 2008). In pediatric AML, 3q26-rearrangements are rare and the role of EVI1 is unknown. In this study, we investigated the frequency and clinical relevance of EVI1+ in pediatric AML. EVI1 expression was analyzed in 233 pediatric AML patients, of whom microarray gene expression profiling data were available. EVI1+ was found in 25 pediatric AML patients (11%), and confirmed with real-time quantitative PCR. This included 13/49 (26%) patients with MLL-rearranged AML: 5/22 (23%) cases with t(9;11); and all (n=4) cases with t(6;11). Moreover, EVI1+ was found in 4/7 (57%) cases with AML M7; in 2/3 (66%) cases with AML M6; in both cases with monosomy 7; in 1/43 (2%) cases with normal cytogenetics; in 2 patients with random cytogenetics, and in 1 patient with a cytogenetic failure. EVI1+ was not found in the t(8;21), inv(16) and t(15;17) subgroups. 3/25 EVI1+ patients lacked the MDS/EVI1 transcript, but no cryptic 3q26-rearrangements were detected with FISH. Molecular analysis showed that one patient had a CEBPα mutation; one patient had an FLT3-ITD; and 3 patients showed a mutation in the RAS oncogene. EVI+ was not correlated with sex or white blood cell count. However, the frequency in children younger than 10 years old was twice as high when compared to older children (14% vs 7%, p=0.12). Survival analysis was restricted to the subset of patients who were treated using uniform DCOG and BFM treatment protocols (n=204). In this cohort, EVI1+ patients had a worse 5-years event-free survival (pEFS) compared to patients without EVI1+ (30 vs. 43%, p=0.02). However, multivariate analysis, including cytogenetics (favorable [t(8;21, inv(16), t(15;17)] vs. other), FLT3-ITD, age and WBC, showed that EVI1+ was not an independent prognostic factor for survival. Moreover, within the unfavorable/normal cytogenetic subgroup, there was no difference in outcome between patients with and without EVI1+. We conclude that EVI1+ is found in ~10% of pediatric AML, and highly correlated with specific unfavorable cytogenetic (MLL-rearrangements) and morphologic (FAB M6/7) subtypes. In contrast to adult AML, no 3q26-rearrangements or cryptic inversions were found, and EVI1+ was not an independent prognostic factor. This difference in prognostic relevance may be due to differences in treatment. Alternatively, these results may indicate that EVI1 plays a different role in disease biology between adult and pediatric AML. This is at least suggested by the lack of 3q26 aberrations in pediatric AML.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4191-4191
Author(s):  
Kathleen Wren Phelan ◽  
Sucha Nand ◽  
Laura C Michaelis

Abstract Abstract 4191 Background: Performance status is traditionally used to judge fitness in cancer patients. It is often a key factor in determining appropriateness for chemotherapy and entry into clinical trials. Most research on PS has been in solid tumor patients, but it is generally assumed to be valid in hematologic malignancies as well. However, PS assessment can be problematic, especially in patients who have become ill quickly or where there are conflicting parameters; e.g. patients whose function is limited but who are still actively working. We explored the role of PS in patients with AML to determine if alternative, more objectively determined parameters, could predict PS. We evaluated the relationship between PS and rates of complete remission (CR) and duration of overall survival (OS) as well as the relationship between objectively determined pretreatment parameters and these outcomes. Methods: Approval for retrospective data collection was obtained by the institutional IRB. A randomly selected cohort of 145 patients with newly diagnosed AML was identified using pharmacy records of treatment with induction agents cytarabine, daunorubicin or azacitidine. We excluded patients with acute promyelocytic leukemia. Pretreatment data was collected from the electronic medical record of each subject, including AML subtype, age, gender, PS, presence of infection at diagnosis, peripheral blood white blood cell count, peripheral blood blast percentage, hemoglobin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, creatinine, albumin, left ventricular ejection fraction (LVEF), bone marrow cellularity, bone marrow blast percentage and cytogenetics. Achievement of complete remission was assessed and overall survival was calculated in months from diagnosis to either death or date of censorship. PS was obtained from physician notes and documented as a Zubrod score. In the absence of documentation, the authors reviewed medical records for presenting symptoms, mobility and functional status and made an assignment. Retrospective assignment of PS was reviewed and confirmed by at least two of the authors. Logistic regression was performed to examine the relationship between pretreatment characteristics and CR, and the effect of pretreatment characteristics and the assignment of PS, dichotomized as good (0–1) vs. poor (2–4). Linear regression analysis was used to investigate the relationship between pretreatment characteristics and OS. Results: A total of 120/145 (83%) were assigned a PS of 0, 1. Twenty patients were considered to have a PS of 2 and five patients had a PS of 3. There was a statistically significant relationship between a good PS assignment and a higher albumin level (OR 5.32, p=0.000, 95% CI 2.32, 12.22). There was no significant relationship between the remaining clinical parameters and PS assignment, including age at diagnosis. Ninety-three patients (64%) achieved a CR. There was no relationship between PS, assigned either contemporarily or retrospectively, with the achievement of CR. The median overall survival was 15 months (range 0 to 92 months). PS did not predict the duration of OS. As is well reported, CR was significantly more likely in younger (< 60 yrs) patients and patients with favorable cytogenetics. Median OS was also prolonged in these patients. No additional pretreatment characteristics were significantly related to CR or OS except LVEF. Patients with an LVEF greater than 50% were more likely to achieve a CR (P=0.0001) and had a longer OS. Conclusions: We found that, among pretreatment characteristics, a higher albumin level was associated with a good performance status. Age was not a predictor of PS. Contrary to expectations, in this population of treated AML patients, PS did not predict either CR or OS. In addition to the association of younger age and favorable cytogenetics with better outcomes, we found that a higher LVEF is also associated with higher CR rates, but this is likely explained by choice of chemotherapeutic agents. Our data calls into question the use of PS as a tool to guide therapy in routine clinical management of acute myeloid leukemia. Prospective studies should evaluate the utility of more objective and more reliably documented clinical parameters than PS for predicting patient outcome. Disclosures: No relevant conflicts of interest to declare.


Oncotarget ◽  
2017 ◽  
Vol 8 (29) ◽  
pp. 47103-47109 ◽  
Author(s):  
Valérie Vidal ◽  
Guillaume Robert ◽  
Laure Goursaud ◽  
Laetitia Durand ◽  
Clemence Ginet ◽  
...  

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