Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk

Schoen, Martin W.; Woelich, Susan K.; Braun, James T.; Reddy, Dhinesh V.; Fesler, Mark; Petruska, Paul J.; Freter, Carl E.; Lionberger, Jack M.

doi:10.1016/j.leukres.2018.03.005

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…In multivariate analysis, age ≥60 years and BM blasts ≥70% were also independent risk factors for AML patients, consistent with previous findings that older AML patients generally have unfavorable prognosis due to poorer baseline performance status, higher mutation burden, and poorer tolerance to chemotherapy, and that abnormal proliferation of BM blasts has apparent adverse effects on survival [39,40]. We found that mutations in DNMT3A and TP53 were also independent risk factors for AML patients, consistent with other studies [41,42].…”

Section: Discussionsupporting

confidence: 91%

Prognostic value of the FUT family in acute myeloid leukemia

et al. 2019

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Genetic abnormalities are more frequently viewed as prognostic markers in acute myeloid leukemia (AML) in recent years. Fucosylation, catalyzed by fucosyltransferases (FUTs), is a post-translational modification that widely exists in cancer cells. However, the expression and clinical implication of the FUT family (FUT1-11) in AML has not been investigated. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and FUT1-11 expression data were included in our study. In patients who received chemotherapy alone showed that high expression levels of FUT3, FUT6, and FUT7 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P < 0.05), whereas high FUT4 expression had favorable effects on EFS and OS (all P < 0.01). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in EFS between the high and low FUT3 expression subgroups (P = 0.047), while other FUT members had no effect on survival. Multivariate analysis confirmed that high FUT4 expression was an independent favorable prognostic factor for both EFS (HR = 0.423, P = 0.001) and OS (HR = 0.398, P < 0.001), whereas high FUT6 expression was an independent risk factor for both EFS (HR = 1.871, P = 0.017) and OS (HR = 1.729, P = 0.028) in patients who received chemotherapy alone. Moreover, we found that patients with low FUT4 and high FUT6 expressions had the shortest EFS and OS (P < 0.05). Our study suggests that high expressions of FUT3/6/7 predict poor prognosis, high FUT4 expression indicates good prognosis in AML; FUT6 and FUT4 have the best prognosticating profile among them, but their effects could be neutralized by allo-HSCT.

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Section: Discussionsupporting

confidence: 91%

Prognostic value of the FUT family in acute myeloid leukemia

et al. 2019

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“…Using PharmGkb, the SNPs of rs5030743 and rs1130609 were identified, which can be treated with cladribine and cytarabine (Table IV). Notably, cladribine is used for hairy cell leukemia, acute myeloid leukemia and chronic lymphocytic leukemia (41–43) while cytarabine is a chemotherapeutic drug utilized for various types of cancer, such as breast and lung cancer (44,45). Cytarabine, similar to gemcitabine, is activated and metabolized by deoxycytidine kinase and cytidine deaminase (46).…”

Section: Resultsmentioning

confidence: 99%

Reconstruction and analysis of circRNA‑miRNA‑mRNA network in the pathology of cervical cancer

Liu

et al. 2019

Oncol Rep

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The present study was performed with the aim of understanding the mechanisms of pathogenesis and providing novel biomarkers for cervical cancer by constructing a regulatory circular (circ)RNA-micro (mi)RNA-mRNA network. Using an adjusted P-value of <0.05 and an absolute log value of fold-change >1, 16 and 156 miRNAs from GSE30656 and The Cancer Genome Atlas (TCGA), 5,321 mRNAs from GSE63514, 4,076 mRNAs from cervical squamous cell carcinoma and endocervical adenocarcinoma (from TCGA) and 75 circRNAs from GSE102686 were obtained. Using RNAhybrid, Venn and UpSetR plot, 12 circRNA-miRNA pairs and 266 miRNA-mRNA pairs were obtained. Once these pairs were combined, a circRNA-miRNA-mRNA network with 11 circRNA nodes, 4 miRNA nodes, 153 mRNA nodes and 203 edges was constructed. By constructing the protein-protein interaction network using Molecular Complex Detection scores >5 and >5 nodes, 7 hubgenes (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) were identified. By mapping the 7 hubgenes into the preliminary circRNA-miRNA-mRNA network, a circRNA-miRNA-hubgenes network consisting of 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519), 2 mRNAs (hsa-miR-15b and hsa-miR-106b) and 7 mRNAs (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) was constructed. There were 22 circRNA-miRNA-mRNA regulatory axes identified in the subnetwork. By analyzing the overall survival for the 7 hubgenes using the Gene Expression Profiling Interactive Analysis tool, higher expression of RRM2 was demonstrated to be associated with a significantly poorer overall survival. PharmGkb analysis identified single nucleotide polymorphisms (SNPs) of rs5030743 and rs1130609 of RRM2, which can be treated with cladribine and cytarabine. RRM2 was also indicated to be involved in the gemcitabine pathway. The 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519) may function as competing endogenous RNAs and serve critical roles in cervical cancer. In addition, cytarabine may produce similar effects to gemcitabine and may be an optional chemotherapeutic drug for treating cervical cancer by targeting rs5030743 and rs1130609 or other similar SNPs. However, the specific mechanism of action should be confirmed by further study.

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“…Apoptosis is a form of programmed cell death comprising the death receptor pathway and the mitochondrial pathway [15] . Mitochondria are the power house within eukaryotic cells as a significant regulator in cell survival, proliferation, apoptosis, metastasis and other activities in a variety of malignant tumor cells including lung, breast and prostate cancers.…”

Section: Resultsmentioning

confidence: 99%

Tanshinone IIA Induces Apoptosis of Leukemia Cancer Cells and Inhibits Tumor Growth In Vivo Through Mitochondrial Pathway

Deng¹,

Tian²,

Chen³

2022

IJPS

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To investigate the effect of Tanshinone IIA on apoptosis of leukemic cancer cells and tumor growth inhibition in vivo. Human leukemia cell line HL-60 cells were divided into model group, low-dose group, medium dose group and high-dose group and transfected according to the groups. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide method was used to calculate the inhibition rate of cell growth, flow cytometry was used to detect the apoptosis rate and mitochondrial membrane potential and Western blot was used to detect mitochondrial membrane potential related protein. The treatment group was treated with Tanshinone IIA and the control group was given phosphate-buffered saline+dimethyl sulfoxide intraperitoneal injection. 2 w later, the tumor size and weight were measured and weighed. The 24 h and 48 h proliferation inhibition rates of the experimental group were significantly higher than those of the model group and increased with the increase of the dose (p<0.05). The early apoptosis rate and late apoptosis rate of the experimental group were significantly higher than those of the model group and increased with the increase of the dose (p<0.05). The level of integral optical density in the experimental group was significantly lower than that in the model group and decreased with the increase of the dose (p<0.05). The levels of caspase-9, caspase-3 and B-cell lymphoma 2 related X protein in the experimental group were significantly higher than those in the model group, while the level of B-cell lymphoma 2 in the experimental group was significantly lower than that in the model group and there was drug dependence (p<0.05). The tumor size and weight of the treatment group were significantly lower than those of the control group (p<0.05). Tanshinone IIA can induce apoptosis and tumor growth of leukemia cancer cells in vivo and slow down the proliferation of cancer cells, which may be related to the regulation of mitochondrial pathway and the inhibition of mitochondrial membrane potential related protein.

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Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk

Cited by 7 publications

References 35 publications

Prognostic value of the FUT family in acute myeloid leukemia

Prognostic value of the FUT family in acute myeloid leukemia

Reconstruction and analysis of circRNA‑miRNA‑mRNA network in the pathology of cervical cancer

Tanshinone IIA Induces Apoptosis of Leukemia Cancer Cells and Inhibits Tumor Growth In Vivo Through Mitochondrial Pathway

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