Survivin and aven: two distinct antiapoptotic signals in acute leukemias

Paydaş, Semra; Tanrıverdi, Kahraman; Yavuz, Sinan; Dişel, Umut; Şahin, Berksoy; Burgut, Refik

doi:10.1093/annonc/mdg277

Cited by 48 publications

(30 citation statements)

References 31 publications

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“…We used flowcytometry for detection of intracellular survivin and determine its MFI on leukemic blast. In our 30 ALL patients, expression of survivin above the background level in normal hematopoietic cells was detected in 19 (63.3%) of the patients this is similar to what was reported by Troeger et al [20], who detect over expression of survivin in 65% of pediatric ALL patients and higher than Paydas et al [24], who study survivin in 56 leukemia patients (37 AML and 28 ALL) they detected high survivin in 54% of the patients. Survivin expression was significantly elevated in pediatric ALL with a median MFI level of 183 (0-1390) when compared with the level in control group (P = 0.003) this in agreement with Troeger et al [20], and with what reported previously as surviving was expressed in all AML cell lines and most of the leukemia cells and/or bone marrow cells [11].…”

Section: Discussionsupporting

confidence: 89%

Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Esh

Atfy

Azizi

et al. 2011

Indian J Hematol Blood Transfus

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Impaired apoptosis is mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin. Survivin was described in number of different tumors and found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. The aim of this study was to determine survivin in pediatric ALL and compare it with clinical and hematological findings, response to therapy and outcome. Flowcytometry was used for detection of intracellular survivin and determine its mean fluorescence intensity (MFI) in bone marrow mononuclear cells. Patients were followed up for 28 months after induction therapy. Survivin was detected in 63.3% of the patients BM. In spite of no association of survivin levels with established risk factors (P [ 0.05) except with high WBC, there was significant higher level of survivin expression in high risk group patients when patients were stratified into high and standard risk groups. According to response to induction therapy, there was no significant difference, in survivin level between patients who achieved CR, RD and ED. However, patients suffering relapse of the disease, had a significant higher basal level of survivin than patients still in remission. Over expression of survivin is a candidate parameter to determine poor prognosis in ALL patients and it may serve to refine treatment stratification with intensification of therapy in those patients prone to relapse.

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Section: Discussionsupporting

confidence: 89%

Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Esh

Atfy

Azizi

et al. 2011

Indian J Hematol Blood Transfus

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“…The genetic lesion identified in AVEN is of potential interest because this gene impairs Apaf-1-mediated activation of caspases, and thus apoptosis (39). We and others (9,(15)(16)(17)40) have previously identified other (non-Bcl-2) antiapoptotic survival pathways as being particularly important in MPM tumorigenesis and drug resistance, and AVEN was recently implicated in acute leukemias (41). Elucidating the functional relevance of the previously uncharacterized variant alleles rendered homozygous by LOH in MPM (Table 3) is a promising avenue for further exploration.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing of malignant pleural mesothelioma tumors

Sugarbaker

Richards²,

Gordon³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

139

116

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Cancers arise by the gradual accumulation of mutations in multiple genes. We now use shotgun pyrosequencing to characterize RNA mutations and expression levels unique to malignant pleural mesotheliomas (MPMs) and not present in control tissues. On average, 266 Mb of cDNA were sequenced from each of four MPMs, from a control pulmonary adenocarcinoma (ADCA), and from normal lung tissue. Previously observed differences in MPM RNA expression levels were confirmed. Point mutations were identified by using criteria that require the presence of the mutation in at least four reads and in both cDNA strands and the absence of the mutation from sequence databases, normal adjacent tissues, and other controls. In the four MPMs, 15 nonsynonymous mutations were discovered: 7 were point mutations, 3 were deletions, 4 were exclusively expressed as a consequence of imputed epigenetic silencing, and 1 was putatively expressed as a consequence of RNA editing. Notably, each MPM had a different mutation profile, and no mutated gene was previously implicated in MPM. Of the seven point mutations, three were observed in at least one tumor from 49 other MPM patients. The mutations were in genes that could be causally related to cancer and included XRCC6, PDZK1IP1, ACTR1A, and AVEN.DNA sequencing ͉ tumor mutations ͉ lung cancer ͉ bioinformatics ͉ loss of heterozygosity B ecause cancer arises as a consequence of multiple mutations, human cancer genomes are being sequenced to identify the mechanisms of tumorigenesis. Pilot sequencing studies include recent exon resequencing of tumors and cell lines that revealed somatic mutations in hundreds of genes not previously implicated in oncogenesis. These studies generally focused on a single class of mutations such as point mutations in coding regions of preselected candidate genes, and the results so far indicate that even within similar histological classes, tumors possess unique mutational profiles (1-3). However, there has rarely been an analysis of whether a mutated gene is actually expressed in the tumor cell nor has there been an attempt to use sequencing to identify other types of mutations such as chromosomal deletions or translocation (4, 5) or loss of heterozygosity related to epigenetic silencing (6, 7). Moreover, no unbiased deep sequencing analysis of all expressed genes in cancer tissues has been reported to date.Malignant pleural mesothelioma (MPM) is an asbestosrelated, rapidly fatal cancer. Its genetic basis is unknown but appears to involve multiple types of chromosomal abnormalities (5,(8)(9)(10)(11)(12)(13)(14). Central mechanisms underlying MPM are unclear, although MPM tumors evoke a strong inflammatory response thought to contribute to tumorigenesis (15). In addition, tumor cell survival promoted by TNF-␣ responsive antiapoptotic proteins such as Inhibitor of Apoptosis-1 (IAP-1) facilitates the resistance of MPM to most cytotoxic chemotherapeutic drugs (16). Expression profiling with microarrays has supported the general role of inflammation in MPM etiology and has provided...

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“…54,55 Furthermore, evidence is now accumulating that the expression level of survivin contributes to the clinical outcome of tumors, including prognosis, susceptibility to anti-cancer drugs, and malignant behavior. 56,57 Recent studies indicate the potential clinical relevance of survivin quantified by real-time PCR in ATL. 58 Selectivity of expression and biological importance render survivin an attractive target for treatment, but the 3-dimensional structure of survivin shows no obvious opportunity for drug design.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax

Kawakami

Tomita

Matsuda

et al. 2005

Intl Journal of Cancer

142

112

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Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. We previously reported the survivin expression profile in ATL, a CD4-positive T-cell malignancy caused by HTLV-I. HTLV-I Tax is thought to play an important role in immortalization of T cells. We have shown also that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by deprivation of IL-2 and converted its growth from being IL-2 dependent to being IL-2 independent through the NF-kB pathway. In our study, we demonstrate that constitutive expression of survivin was associated with resistance to apoptosis after IL-2 deprivation in Tax-expressing CTLL-2 cells. Transient transfection assays showed that survivin promoter was transactivated by Tax, via the activation of NF-kB. Pharmacological NFkB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax-expressing CTLL-2 cells. Our findings suggest that activated NF-kB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin. ' 2005 Wiley-Liss, Inc.

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Survivin and aven: two distinct antiapoptotic signals in acute leukemias

Cited by 48 publications

References 31 publications

Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Transcriptome sequencing of malignant pleural mesothelioma tumors

Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax

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