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BIRC5 (survivin) splice variant expression correlates with refractory disease and poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group.


ABSTRACT: The inhibitor-of-apoptosis protein survivin, encoded by BIRC5, regulates apoptosis, cell division and proliferation. Several survivin splice variants have been described however, the prognostic significance of their expression has not been well defined in pediatric acute myeloid leukemia (AML).Quantitative expression analyses of BIRC5 mRNA (n?=?306) and survivin transcript splice variants (n?=?90) were performed on diagnostic bone marrow samples from children with de novo AML treated on the clinical trials CCG-2961 and AAML03P1, then correlated with disease characteristics and clinical outcome.Total BIRC5 expression did not correlate with clinical outcome. Fragment length analysis and sequencing of the entire BIRC5 transcript demonstrated three splice variants. The most prominent product, wild-type survivin, was expressed in all samples tested. Two minor transcripts were present in 90 patients treated on CCG-2961; survivin-2B and a novel variant, survivin-?Ex2, characterized by deletion of BIRC5 exon II. A high 2B/?Ex2 expression ratio (?1) correlated with increased diagnostic WBC count, monocytic phenotype, +8 cytogenetics, lower complete remission (45% [n?=?10] vs. 88% [n?=?59], P?

SUBMITTER: Moore AS 

PROVIDER: S-EPMC4285339 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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BIRC5 (survivin) splice variant expression correlates with refractory disease and poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group.

Moore Andrew S AS   Alonzo Todd A TA   Gerbing Robert B RB   Lange Beverly J BJ   Heerema Nyla A NA   Franklin Janet J   Raimondi Susana C SC   Hirsch Betsy A BA   Gamis Alan S AS   Meshinchi Soheil S  

Pediatric blood & cancer 20131011 4


<h4>Background</h4>The inhibitor-of-apoptosis protein survivin, encoded by BIRC5, regulates apoptosis, cell division and proliferation. Several survivin splice variants have been described however, the prognostic significance of their expression has not been well defined in pediatric acute myeloid leukemia (AML).<h4>Procedure</h4>Quantitative expression analyses of BIRC5 mRNA (n = 306) and survivin transcript splice variants (n = 90) were performed on diagnostic bone marrow samples from children  ...[more]

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