scholarly journals NPM1A in plasma is a potential prognostic biomarker in acute myeloid leukemia

2018 ◽  
Vol 13 (1) ◽  
pp. 236-241
Author(s):  
Chengming Sun ◽  
Yujie Gao ◽  
Liping Yang ◽  
Huiyuan Shao ◽  
Jie li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chi Square ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Healthy Donors ◽  
Chi Square Test ◽  
Ideal Tool ◽  
The Relationship ◽  
Acute Myeloid

AbstractObjectiveThe aim of the study was to investigate whether nucleophosmin type A mutation (NPM1A) in plasma was associated with the prognosis of patients with acute myeloid leukemia (AML).MethodsPlasmaNPM1Alevels were investigated in 80 AML patients, 22 patients with benign hematopathy and 12 healthy donors by qRT-PCR. Additionally, the relationship betweenNPM1Alevels and clinic characteristics were evaluated by Chi-square test. Kaplan-Meier method was used to analyze overall survival (OS) and relapse-free survival (RFS), and univariate and multivariate analyses were performed with Cox proportional hazard model.ResultsPlasma levels ofNPM1Ain AML patients were significantly higher than those in benign hematopathy patients and healthy controls, respectively (both P<0.001). Additionally, highNPM1Alevel was significantly associated with higher WBC and platelet count (both, P<0.05). Moreover, survival analysis revealed that patients with highNPM1Alevels had worse OS (P<0.001) and RFS (P<0.001). Multivariate analysis identifiedNPM1Aas an independent prognostic predictor for AML (OS: HR=8.214, 95% CI: 2.974-22.688, P<0.001; RFS: HR=4.640, 95%CI: 1.825-11.795, P=0.001).ConclusionsResults reveal thatNPM1Ain plasma could serve as an ideal tool for predicting the prognosis of patients with AML.

scholarly journals Effectiveness and Survival of 4 Courses of Chemotheray in 321 Children with Acute Myeloid Leukemia in China: A Multicenter, Nonrandomized Clinical Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2596-2596
Author(s):  
Zheng Yong Zhi ◽  
Jian Li ◽  
Xiaoqin Feng ◽  
Mincui Zheng ◽  
Chunfu Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Chi Square ◽  
Chi Square Test ◽  
Group A ◽  
Childhood Aml ◽  
Independent Risk Factors ◽  
Group B ◽  
Acute Myeloid

Objectives Increasing the intensity of chemotherapy can improve long-term survival in young patients with acute myeloid leukemia, but the number of appropriate courses is still worth exploring. We prospectively used MRC-AML 15 protocol as backbone to designed the C-HUANAN-AML15 protocol, which including 2 courses of inductions and 2 courses of consolidation to treat new diagnosed acute myeloid leukemia children in order to adapt to China's actual situation. The midterm outcome of effectiveness and survival was analyzed in the multicenter of south of China. Patients and methods Total of 321 newly diagnosed childhood AML patients from 9 centers of south of China from November 2014 to December 2018 were included in the study. 194 boys and 127 girls, with median age 6 (0.5-14) years old were enrolled. The median follow-up period was 16 (4 to 73) months up to July 2019. Risk stratifications were based on genetic abnormalities and response to induction chemotherapy . One hundred and seven patients (33.3%),146 patients (45.5%),68 patients (21.2%) were classified as low-risk group (LR), intermediate-risk group (IR) and high-risk group (HR) respectively. The protocol C-HUANAN-AML15 protocol including tandem 2 courses of FLAG-IDA regimen (marked as group A, n=225) , or sequential DAE(3+5+10) and DAE(3+5+8) regimen (marked as group B, n=96) were applied to induction chemotherapy. One course of Homoharringtonine (substitution of Amsacrine in MRC-AML 15 protocol)/ Cytarabine/ Etoposide and one course of Mitoxantrone/ Cytarabine in consolidation chemotherapy were uniform in both groups. 57 patients (39 patients in group A and 18 patients in group B, P=0.752) selected hematopoietic stem cell transplantation (HSCT) after 2-3 courses of chemotherapy. In the 264 patients who only underwent chemotherapy, the LR/IR/HR ratio in the A and B group was 65(34.9%),82(44.1%),39(21.0%) and 34(43.6%),37(47.4%),7(9.0%) respectively (P=0.056). The similarity of clinical data was analyzed by the chi square test and COX proportional hazard function model. Complete remission (CR) rates, treatment related mortalities (TRM), event-free survival (EFS) and overall survival (OS) were compared by Log-Rank chi square test. Results The CR rates in A and B group were 87.6% and 83.3% after 1st course induction regimen, and 92.4% and 89.2% after 2nd course induction regimen, which were not significantly different (P=0.375, 0.337). The 3-year EFS and OS of all patients were 65.8±3.2% and 70.3±3.4% respectively. The 3-year EFS and OS of 264 patients who only received chemotherapy was 65.4±7.4% and 71.7±3.4%. The 3-year EFS of HR, IR and LR in patients who received only chemotherapy were 40.3±8.8%, 62.0±5.2% and 83.5±4.3% respectively (P=0.000). The 3-year OS of HR, IR and LR in patients who received only chemotherapy were 46.9±9.0%, 69.1±5.1% and 86.1±4.0% respectively (P=0.000). The 3-year EFS of A and B group in patients who received only chemotherapy was 70.8±4.0% and 56.7±6.3% (P=0.059); The 3-year OS of A and B group in patients who received only chemotherapy was 78.7±3.6% and 58.6±6.4% (P=0.005). The 3-year EFS and OS of 57 patients who received HSCT was 60.2±8.9% and 65.4±7.4%(P=0.477, 0.821). The EFS of IR and HR patients who received HSCT were superior than that of who received only chemotherapy, but they were not significantly different (78.6±8.6%vs62.4±5.1%, P=0.121; 44.4±12.9%vs38.9±8.8%, P=0.208). Univariate analysis showed that initial white blood cell count (≥50×109/L), RUNX1-RUNX1T1 fusion gene, EVI1 gene positive, FLT3-ITD mutation, no CR after 1st course and 2nd course induction affected 3-year EFS (all P<0.05). Multivariate prognostic analysis with COX proportional hazard function model for EFS showed that EVI1 gene (HR0.397, 95%CI 0.201-0.785, P=0.008) and no CR after 2nd course induction (HR0.319, 95%CI 0.134-0.763, P=0.010) were independent risk factors. Conclusion This prospectively clinical study indicated that intensive induction with FLAG-IDA or DAE followed only 2 courses of consolidation chemotherapy was effective in the LR and IR group, and could be utilized as first line treatment in childhood AML. EVI1 gene positive and no CR after 2nd induction course were independent risk factors for EFS. More effective strategies are needed to be explored for HR group patients, EVI1 gene positive patients and those who cannot achieve CR after 2nd course induction. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Liu ◽  
Jin-Mou Yi ◽  
Yi Liu ◽  
Cong Chen ◽  
Kai-Xuan Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Prognostic Biomarker ◽  
Mrna Levels ◽  
Kaplan Meier ◽  
Healthy Donors ◽  
Enhancer Binding Protein ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (CDK6), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of CDK6 were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, CDK6 expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of CDK6 was tightly correlated with peripheral blood blasts, French–American–British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of CDK6 expression on the prognosis of non-APL AML patients remain uncertain. We found that CDK6 expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan–Meier analysis. CDK6 was also found to be positively associated with genes identified to contribute to the development of leukemia, including CCND2, DNMT3B, SOX4, and IKZF2, as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that CDK6 might be a potential diagnostic and prognostic biomarker in non-APL AML patients.

scholarly journals Decitabine shows anti-acute myeloid leukemia potential via regulating the miR-212-5p/CCNT2 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 1013-1023
Author(s):  
Lina Xing ◽  
Jinhai Ren ◽  
Xiaonan Guo ◽  
Shukai Qiao ◽  
Tian Tian
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
Polymerase Chain ◽  
The Relationship ◽  
Acute Myeloid

AbstractPrevious research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.

Long-Term Prognosis of Acute Myeloid Leukemia According to the New Genetic Risk Classification of the European LeukemiaNet Recommendations: Evaluation of the Proposed Reporting System

2011 ◽  
Vol 29 (20) ◽  
pp. 2758-2765 ◽  
Author(s):  
Christoph Röllig ◽  
Martin Bornhäuser ◽  
Christian Thiede ◽  
Franziska Taube ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reporting System ◽  
Young Patients ◽  
Risk Classification ◽  
Rank Test ◽  
Kaplan Meier ◽  
Heterogenous Group ◽  
Long Term Prognosis ◽  
Acute Myeloid

Purpose The current European LeukemiaNet (ELN) recommendations for acute myeloid leukemia (AML) propose a new risk reporting system, integrating molecular and cytogenetic factors and subdividing the large heterogenous group of intermediate-risk patients into intermediate-I (IR-I) and intermediate-II (IR-II). We assessed the prognostic value of the new risk classification in a large cohort of patients. Patients and Methods Complete data for classification were available for 1,557 of 1,862 patients treated in the AML96 trial. Patients were assigned to the proposed genetic groups from the ELN recommendations, and survival analyses were performed using the Kaplan-Meier method and log-rank test for significance testing. Results The median age of all patients was 67 years. With a median follow-up of 8.3 years, significant differences between all risk categories were observed in patients age ≤ 60 years regarding the time to relapse, relapse-free survival, and overall survival (OS). Patients in the IR-II group had a better prognosis than patients in the IR-I group. The median OS times in young patients with favorable risk (FR), IR-I, IR-II, and adverse risk (AR) were 5.3, 1.1, 1.6, and 0.5 years, respectively. Separate analyses in the age group older than 60 years revealed significant differences between FR, AR, and IR as a whole, but not between IR-I and IR-II. Conclusion In younger patients with AML, the ELN classification seems to be the best available framework for prognostic estimations to date. Caution is advised concerning its use for prospective treatment allocation before it has been prospectively validated. In elderly patients, alternative prognostic factors are desirable for further risk stratification of IR.

scholarly journals High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1517-1524 ◽  
Author(s):  
Marjan J. T. Veuger ◽  
M. Willy Honders ◽  
Jim E. Landegent ◽  
Roel Willemze ◽  
Renée M. Y. Barge
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Deoxycytidine Kinase ◽  
Wild Type ◽  
Healthy Donors ◽  
Alternatively Spliced ◽  
Acute Myeloid

Deficiency of functional deoxycytidine kinase (dCK) is a common characteristic for in vitro resistance to cytarabine (AraC). To investigate whether dCK is also a target for induction of AraC resistance in patients with acute myeloid leukemia (AML), we determined dCK messenger RNA (mRNA) expression in (purified) leukemic blasts and phytohemagglutinin-stimulated T cells (PHA T cells) from patients with chemotherapy-sensitive and chemotherapy-resistant AML. In control samples from healthy donors (PHA T cells and bone marrow), only wild-type dCK complementary DNA (cDNA) was amplified. Also, in (purified) leukemic blasts from patients with sensitive AML, only wild-type dCK cDNAs were observed. These cDNAs coded for active dCK proteins in vitro. However, in 7 of 12 (purified) leukemic blast samples from patients with resistant AML, additional polymerase chain reaction fragments with a deletion of exon 5, exons 3 to 4, exons 3 to 6, or exons 2 to 6 were detected in coexpression with wild-type dCK. Deletion of exons 3 to 6 was also identified in 6 of 12 PHA T cells generated from the patients with resistant AML. The deleted dCK mRNAs were formed by alternative splicing and did code for inactive dCK proteins in vitro. These findings suggest that the presence of inactive, alternatively spliced dCK mRNA transcripts in resistant AML blasts may contribute to the process of AraC resistance in patients with AML.

scholarly journals Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Liver Hepatocellular Carcinoma ◽  
The Relationship

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

Relationship Between Cleaved L-Selectin Levels and the Outcome of Acute Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3115-3122 ◽  
Author(s):  
M. Extermann ◽  
M. Bacchi ◽  
N. Monai ◽  
M. Fopp ◽  
M. Fey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Plasma ◽  
Multivariate Statistical ◽  
Free Survival ◽  
The Mean ◽  
American Society ◽  
The Relationship ◽  
Acute Myeloid

Abstract High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels ≥3.12 μg/mL (≥3 SD above the mean of healthy controls: “increased”). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P &lt; .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with “normal” sL-selectin levels had higher probability of achieving complete remission (CR) than with “increased” levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), “normal” sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58;P = .03). Moreover, patients with “increased” sL-selectin levels (≥3.12 μg/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin &lt;3.12 μg/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis. © 1998 by The American Society of Hematology.

scholarly journals High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1517-1524 ◽  
Author(s):  
Marjan J. T. Veuger ◽  
M. Willy Honders ◽  
Jim E. Landegent ◽  
Roel Willemze ◽  
Renée M. Y. Barge
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Deoxycytidine Kinase ◽  
Wild Type ◽  
Healthy Donors ◽  
Alternatively Spliced ◽  
Acute Myeloid

Abstract Deficiency of functional deoxycytidine kinase (dCK) is a common characteristic for in vitro resistance to cytarabine (AraC). To investigate whether dCK is also a target for induction of AraC resistance in patients with acute myeloid leukemia (AML), we determined dCK messenger RNA (mRNA) expression in (purified) leukemic blasts and phytohemagglutinin-stimulated T cells (PHA T cells) from patients with chemotherapy-sensitive and chemotherapy-resistant AML. In control samples from healthy donors (PHA T cells and bone marrow), only wild-type dCK complementary DNA (cDNA) was amplified. Also, in (purified) leukemic blasts from patients with sensitive AML, only wild-type dCK cDNAs were observed. These cDNAs coded for active dCK proteins in vitro. However, in 7 of 12 (purified) leukemic blast samples from patients with resistant AML, additional polymerase chain reaction fragments with a deletion of exon 5, exons 3 to 4, exons 3 to 6, or exons 2 to 6 were detected in coexpression with wild-type dCK. Deletion of exons 3 to 6 was also identified in 6 of 12 PHA T cells generated from the patients with resistant AML. The deleted dCK mRNAs were formed by alternative splicing and did code for inactive dCK proteins in vitro. These findings suggest that the presence of inactive, alternatively spliced dCK mRNA transcripts in resistant AML blasts may contribute to the process of AraC resistance in patients with AML.

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