Back to Search
Start Over
Significance of expression of ITGA5 and its splice variants in acute myeloid leukemia: a report from the Children's Oncology Group.
- Source :
-
American journal of hematology [Am J Hematol] 2013 Aug; Vol. 88 (8), pp. 694-702. Date of Electronic Publication: 2013 Jun 20. - Publication Year :
- 2013
-
Abstract
- Acute myeloid leukemia (AML) encompasses a heterogeneous group of diseases, and novel biomarkers for risk refinement and stratification are needed to optimize patient care. To identify novel risk factors, we performed transcriptome sequencing on 68 diagnostic AML samples and identified 2 transcript variants (-E2 and -E2/3) of the α-subunit (ITGA5) of the very late antigen-5 integrin. We then quantified expression of ITGA5 and these splice variants in specimens from participants of the AAML03P1 trial. We found no association between ITGA5 expression and clinical outcome. In contrast, patients with the highest relative expression (Q4) of the -E2/3 ITGA5 splice variant less likely had low-risk disease than Q1-3 patients (21% vs. 38%, P = 0.027). Q4 patients had worse response to chemotherapy with a higher proportion having persistent minimal residual disease (50% vs. 23%, P = 0.003) and inferior overall survival (at 5 years: 48% vs. 67%, P = 0.015); the latter association was limited to low-risk patients (Q4 vs. Q1-3: 56% vs. 85%, P = 0.043) and was not seen in standard-risk (51% vs. 60%, P = 0.340) or high-risk (33% vs. 38%, P = 0.952) patients. Our exploratory studies indicate that transcriptome sequencing is useful for biomarker discovery, as exemplified by the identification of ITGA5 -E2/3 splice variant as potential novel adverse prognostic marker for low-risk AML that, if confirmed, could serve to further risk-stratify this patient subset.<br /> (Copyright © 2013 Wiley Periodicals, Inc.)
- Subjects :
- Adult
Child
Child, Preschool
Disease-Free Survival
Female
Humans
Infant
Infant, Newborn
Male
Risk Factors
Survival Rate
Biomarkers, Tumor biosynthesis
Biomarkers, Tumor genetics
Gene Expression Regulation, Leukemic genetics
Integrin alpha5 biosynthesis
Integrin alpha5 genetics
Leukemia, Myeloid, Acute drug therapy
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute metabolism
Leukemia, Myeloid, Acute mortality
RNA Splicing genetics
Transcriptome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-8652
- Volume :
- 88
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- American journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 23686445
- Full Text :
- https://doi.org/10.1002/ajh.23486