Optimal Therapy for Adult Patients with Acute Myeloid Leukemia in First Complete Remission

Wiernik, Peter H.

doi:10.1007/s11864-014-0281-9

Cited by 7 publications

(3 citation statements)

References 65 publications

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“…At present, the treatment of AML is mainly chemotherapy. Most of the first diagnosed patients can get complete remission (CR) after combined chemotherapy, but the recurrence rate is as high as 70% [ 5 ]. The drug resistance, recurrence, and side effects during chemotherapy keep the mortality at a high peak.…”

Section: Introductionmentioning

confidence: 99%

The Regulation of circRNA RNF13/miRNA-1224-5p Axis Promotes the Malignant Evolution in Acute Myeloid Leukemia

Zhang

Wang

et al. 2020

BioMed Research International

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Objective. To study the biological function of circular RNA RNF13 (circRNF13) in acute myeloid leukemia (AML) and its relationship with prognosis. Methods. We constructed stable AML cell lines with downregulated expression of circRNF13, and then, we explored the effect of downregulation of circRNF13 expression on the proliferation, migration, and invasion through qRT-PCR, MTT curve, colony formation, transwell migration and invasion experiment, cell cycle, apoptosis, Caspase 3/7 assay, and other experiments. We also studied the expression of C-myc and Tenascin-C by qRT-PCR to explore the role of circRNF13. Results. When the expression of circRNF13 was downregulated, the proliferation rate of AML cells decreased significantly, the cell cycle was blocked to G1 phase, and apoptosis rate increased significantly. C-myc related to cell proliferation decreased significantly at RNA level. Furthermore, when the expression of circRNF13 was downregulated, the migration and invasion ability of AML cells was significantly reduced, and the expression of Tenascin-C related to migration and invasion also decreased significantly. The luciferase reporter assay system confirmed that miRNA-1224-5p was the direct target of circRNF13. Conclusion. CircRNF13 inhibited the proliferation, migration, and invasion of AML cells by regulating the expression of miRNA-1224-5p. This study provides some clues for the diagnosis and treatment of AML.

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Section: Introductionmentioning

confidence: 99%

The Regulation of circRNA RNF13/miRNA-1224-5p Axis Promotes the Malignant Evolution in Acute Myeloid Leukemia

Zhang

Wang

et al. 2020

BioMed Research International

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“…Cytarabine (Ara-C) is a cytosine analog that is currently indicated for the treatment of acute myeloid leukemia (AML) [1]. Ara-C is a prodrug that requires cellular influx primarily through the human equilibrative nucleoside transporter (hENT1) and active phosphorylation within the cell by the deoxycytidine kinase (dCK) enzyme to produce a monophosphorylated product (dCMP), which is bi- and triphosphorylated to act as an antimetabolite.…”

Section: Introductionmentioning

confidence: 99%

Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine

Candelaria¹,

Corrales-Alfaro²,

Gutiérrez-Hernández³

et al. 2016

Chemotherapy

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Background: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. Methods: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. Results: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. Conclusions: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.

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“…2 Currently, the standard treatment protocol for AML is combination chemotherapy, and patients may also undergo allogeneic stem cell transplantation, especially in high-risk groups for induction failure or recurrence. [3][4][5] Among patients over the age of 60 years, a Overexpression of annexin A5 might guide the gemtuzumab ozogamicin treatment choice in patients with pediatric acute myeloid leukemia complete remission (CR) rate of 40% to 60% can be achieved, though only 5% to 15% can be cured. 1,6 For the large number of AML cases in children and adolescents, overall survival (OS) and CR rates are 67% and 93%, respectively.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of annexin A5 might guide the gemtuzumab ozogamicin treatment choice in patients with pediatric acute myeloid leukemia

Zhang

et al. 2020

Ther Adv Med Oncol

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Background: Acute myeloid leukemia (AML) is a common hematological malignancy. Gemtuzumab ozogamicin (GO), a humanized anti-CD33 antibody conjugated with the potent anti-tumor antibiotic calicheamicin, represents a promising targeted therapy for AML. Annexin A5 (ANXA5) is a proposed marker for the clinical prognosis of AML to guide treatment choice. Methods: In total, 253 patients with pediatric AML were enrolled and divided into two treatment groups: conventional chemotherapy alone and conventional chemotherapy in combination with GO. Univariate, multivariate, and Kaplan–Meier survival analyses were conducted to assess risk factors and clinical outcomes, and to estimate hazard ratios (HRs) and their 95% confidence interval. The level of statistical significance was set at p < 0.05. Results: In the GO treatment group, high ANXA5 expression was considered a favorable prognostic factor for overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that high ANXA5 expression was an independent favorable factor for OS (HR = 0.629, p = 0.084) and EFS (HR = 0.544, p = 0.024) distinct from the curative effect of GO treatment. When all patients were again divided into two groups, this time based on the median expression of ANXA5, patients undergoing chemotherapy combined with GO had significantly better OS ( p = 0.0012) and EFS ( p = 0.0003) in the ANXA5 high-expression group. Gene set enrichment analysis identified a relevant series of pathways associated with glutathione metabolism, leukocyte transendothelial migration, and hematopoietic cell lineage. Conclusion: The expression level of ANXA5 can help optimize the treatment regimen for individual patients, and patients with overexpression of ANXA5 may circumvent poor outcomes from chemotherapy combined with GO.

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Optimal Therapy for Adult Patients with Acute Myeloid Leukemia in First Complete Remission

Cited by 7 publications

References 65 publications

The Regulation of circRNA RNF13/miRNA-1224-5p Axis Promotes the Malignant Evolution in Acute Myeloid Leukemia

The Regulation of circRNA RNF13/miRNA-1224-5p Axis Promotes the Malignant Evolution in Acute Myeloid Leukemia

Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine

Overexpression of annexin A5 might guide the gemtuzumab ozogamicin treatment choice in patients with pediatric acute myeloid leukemia

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