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Significance of expression of ITGA5 and its splice variants in acute myeloid leukemia: a report from the Children's Oncology Group.

Authors :
Walter RB
Laszlo GS
Alonzo TA
Gerbing RB
Levy S
Fitzgibbon MP
Gudgeon CJ
Ries RE
Harrington KH
Raimondi SC
Hirsch BA
Gamis AS
W McIntosh M
Meshinchi S
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.)

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