<i>E2F3a</i> gene expression has prognostic significance in childhood acute lymphoblastic leukemia

Wang, Kai-Ling; Mei, Yanyan; Cui, Lei; Zhao, Xiaoxi; Li, Weijing; Gao, Chao; Jiao, Yanmei; Liu, Feifei; Wu, Min-Yuan; Ding, Wei; Li, Zhigang

doi:10.1111/ejh.12341

Cited by 7 publications

(10 citation statements)

References 27 publications

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“…Abnormal high expression of E2F3a has been found in many types of solid tumors [ 13 , 14 , 19 ], often associated with poor prognosis [ 24 , 25 ]. However, our previous study has shown that E2F3a was generally low-expressed and associated with leukemic relapse or induction failure in childhood ALL [ 20 ]. Accordingly, in present study, we showed that E2F3a over-expression made leukemic cells proliferate more rapidly, and more sensitive to VCR and DNR.…”

Section: Discussionmentioning

confidence: 99%

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Transcription factor E2F3a regulates CASP8AP2 transcription and enhances sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia

Liu¹,

Wang²,

Deng³

et al. 2018

Cancer Cell Int

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BackgroundLow expression of E2F3a and caspase 8 associated protein 2 (CASP8AP2) are associated with poor prognosis of childhood acute lymphoblastic leukemia (ALL).MethodsDual-luciferase reporter assay and wild type as well as four mutated types of reporter plasmids were used to demonstrate the activation of E2F3a on CASP8AP2 transcription. The direct binding of E2F3a with the promoter of CASP8AP2 was shown by Chromatin Immunoprecipitation (ChIP). Cell proliferation activity and cell cycle were determined by MTS and flow cytometry in leukemic cells after treating with common chemotherapeutic drugs vincristine and daunorubicin.ResultsIn this study, we found that up-regulation of E2F3a in leukemic cells led to increased fraction of cells in S and G2/M phase, accelerated proliferation, and enhanced sensitivity to vincristine and daunorubicin. ChIP and luciferase assay indicated that E2F3a could directly bind to two fragments in the wild type of CASP8AP2 promotor (− 206 to − 69 and − 677 to − 507), and activate its transcription activity which was reduced in mutated promotors. The effect of E2F3a on chemotherapeutic sensitivity of leukemic cells could be reversed by down-regulating CASP8AP2.ConclusionsE2F3a could promote transcription and expression of CASP8AP2. The effect of E2F3a on chemotherapeutic sensitivity of ALL cells was implemented by regulating CASP8AP2 expression to a great extent.

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Section: Discussionmentioning

confidence: 99%

“…The latter could be found in G0 phase, whereas E2F3a played a pivotal role in transition of G1/S and cell proliferation [ 19 ]. Our previous study has showed that similar to CASP8AP2 , low expression of E2F3a was common and related to poor treatment outcome in childhood ALL [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Transcription factor E2F3a regulates CASP8AP2 transcription and enhances sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia

Liu¹,

Wang²,

Deng³

et al. 2018

Cancer Cell Int

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“…Between March 2008 and July 2010, 203 children with newly diagnosed ALL were enrolled in the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol at Beijing Children's Hospital. Criteria for patient inclusion were ≥70% leukemic cells in diagnostic bone marrow (BM) samples (16), treatment according to the CCLG-ALL 2008 protocol (17) and sufficient BM sample for total RNA/microRNA (miRNA) extraction. A total of 112 children with ALL were excluded from analysis.…”

Section: Methodsmentioning

confidence: 99%

Low miR‑210 and CASP8AP2 expression is associated with a poor outcome in pediatric acute lymphoblastic leukemia

Mei

Zhang

et al. 2017

Oncol Lett

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The prognostic significance of microRNA (miR)-210 and the caspase 8-associated protein 2 () gene in children with acute lymphoblastic leukemia (ALL) has been validated and has been demonstrated as a target of miR-210. In the present study, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine miR-210 and expression in 91 children with ALL. Associations between gene expression levels and the prognostic value of combined detection of the two indicators were analyzed. Results from a receiver operating characteristic curve demonstrated that threshold values of miR-210 and were 3.8243 and 0.4760, respectively. Although the expression of miR-210 and were not associated at the mRNA level in pediatric ALL, combined detection of the two predicted ALL prognosis with an increased accuracy. Furthermore, an equation was devised including minimal residual disease at day 33 and expression of miR-210 and , which may enable bone marrow relapse to be predicted more precisely compared with the current risk stratification.

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“…As in pediatric leukemia where higher doses of chemotherapy drugs were often applied, better remission in CCR rate can be achieved. However, there are currently no satisfactory makers for the prognosis of disease relapse, even at the time of recurrence [ 29 ]. From the investigation using BCP-ALL patient BM samples, we found that most of the remission patients following treatments exerted reduced levels of coilin and p27 expression comparing to the time at initial diagnosis.…”

Section: Discussionmentioning

confidence: 99%

The prognostic potential of coilin in association with p27 expression in pediatric acute lymphoblastic leukemia for disease relapse

Yue

Gao

et al. 2018

Cancer Cell Int

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BackgroundCajal body (CB) is a nucleic organelle where small nuclear ribonucleoproteins undergo modification, maturation, splicing and/or assembly. Coilin is the marker structural protein of CBs. The expression level and cellular localization of coilin is sensitive to chemotherapeutic reagents, such as cisplatin. The gene of cyclin-dependent kinase inhibitor 1B (p27) is located with a high incidence translocation region of leukemic chromosomes, and its expression was of prognosis values in a variety of adult leukemia types. The exact profile and associated functions of coilin, as well as p27, in children’s acute lymphoblastic leukemia (ALL) is obscure.MethodsBone marrow samples from 144 patients with ALL were collected. The expression levels of coilin and p27 were detected by qRT-PCR. The patient cohort was divided into low and high groups of coilin and p27 respectively. The prognosis and clinicobiological characteristics of different groups were investigated, especially focused on the treatment outcome. Leukemia cells of Reh or RS4;11 were exposed to different concentrations of DNR, prior to the detection for morphological changes of coilin by immunofluorescence. In Reh cells, lentivirus sh-coilin was used to silence coilin expression. Western blotting was used to detect coilin and p27 expression; flow cytometry was used for cell cycle and apoptosis assay; MTS method was used for measuring cell viability to examine the drug sensitivity of DNR.ResultsIn this study, we found that daunorubicin was able to induce significant morphological changes of CBs in Reh and RS4;11 cells. Knockdown the expression of coilin increased the sensitivity to daunorubicin and inhibited the expression of p27 in Reh cells, and led to increased apoptosis. Importantly, not only the levels of coilin and p27 mRNA expression at initial diagnosis ALL children are markedly higher than those at complete remission (CR), but also both coilin and p27 expression in the relapsed patients was observed significantly higher comparing to the continuous CR patients. The 4-year EFS and RFS indicated that low levels of both coilin and p27 group favored better prognosis (p < 0.05).ConclusionsOur results indicated that consideration of coilin and p27 levels could be a prognostic reference for predicting the outcome of pediatric ALL patients, especially for disease recurrence. Reduction of coilin expression was sufficient to increase the sensitivity of leukemic cells to daunorubicin treatments, and during which possibly involved functions of p27 in cell cycle regulation and its effects on cell apoptosis.

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E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia

Abstract: Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification.

Cited by 7 publications

References 27 publications

Transcription factor E2F3a regulates CASP8AP2 transcription and enhances sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia

Transcription factor E2F3a regulates CASP8AP2 transcription and enhances sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia

Low miR‑210 and CASP8AP2 expression is associated with a poor outcome in pediatric acute lymphoblastic leukemia

The prognostic potential of coilin in association with p27 expression in pediatric acute lymphoblastic leukemia for disease relapse

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