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 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 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.

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.

ANP32A Is an Unfavorable Prognostic Biomarker in Cytogenetically Normal Acute Myeloid Leukemia

2019 ◽  
Author(s):  
Sai Huang ◽  
Zhi Huang ◽  
Chao Ma ◽  
Lan Luo ◽  
Yan-fen Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Biomarker ◽  
Acute Myeloid

scholarly journals Functional implications of microRNAs in acute myeloid leukemia by integrating microRNA and messenger RNA expression profiling

Cancer ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 4696-4706 ◽  
Author(s):  
Violaine Havelange ◽  
Nicole Stauffer ◽  
Catherine C. E. Heaphy ◽  
Stefano Volinia ◽  
Michael Andreeff ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Expression Profiling ◽  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Rna Expression ◽  
Functional Implications ◽  
Rna Expression Profiling ◽  
Acute Myeloid

scholarly journals Dysregulation of CCAAT/enhancer binding protein-alpha (CEBPA) expression in the bone marrow of acute myeloid leukemia patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Naglaa M. Hassan ◽  
Fadwa Said ◽  
Roxan E. Shafik ◽  
Mona S. Abdellateif
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Binding Protein ◽  
Response To Treatment ◽  
Pathological Features ◽  
Poor Prognostic Factor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by accumulation of different types of mutations commonly the CCAAT/enhancer binding protein-alpha (CEBPA). However, the dysregulations of CEBPA expression in AML is still a debatable issue. The aim of the current study was to assess CEBPA gene expression in bone marrow (BM) aspiration specimens of 91 AML patients, compared to 20 control donors of bone marrow transplantation (BMT), using RT-PCR. Data were correlated with patients’ clinico-pathological features, response to treatment, progression-free survival (PFS), and overall survival (OS) rates. Results There was overexpression of CEBPA gene in AML patients compared to normal control [1.7 (0.04–25.6) versus 0.17 (0–4.78), respectively, P < 0.001]. Upregulation of CEBPA expression associated significantly with increased BM hypercellularity, total leucocyte counts, peripheral blood blast cell count, and poor PFS (P < 0.001, 0.002, 0.001, and 0.013, respectively). There was no significant association between CEBPA expression and any other relevant clinico-pathological features or OS rates (P = 0.610) of the patients. ROC analysis for biological relevance of CEBPA expression with AML showed that sensitivity and specificity of CEBPA expression at a cut-off value of 0.28 are 92.3% and 78.6%, respectively (P < 0.001). All patients who had CEBPA overexpression and mutant FLT3 showed BM hypercellularity, adverse cytogenetic risk, increased TLC, and PB blast cells count (P = 0.007, P < 0.001, 0.016, and 0.002, respectively). Conclusion CEBPA overexpression could be used as a genetic biological marker for AML diagnosis, as well as a poor prognostic factor for disease progression. It has no impact on OS rates of the patients.

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.

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