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Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia
Author(s) -
Silkjaer Trine,
Nyvold Charlotte Guldborg,
JuhlChristensen Caroline,
Hokland Peter,
Nørgaard Jan Maxwell
Publication year - 2013
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12166
Subject(s) - cytochrome c oxidase , biology , myeloid , protein subunit , univariate analysis , hazard ratio , disease , gene , medicine , mitochondrion , gastroenterology , cancer research , genetics , multivariate analysis , confidence interval
Alterations in the two catalytic genes cytochrome c oxidase subunits I and II ( COI and COII ) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia ( AML ). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML . In 37 (16%) patients, a non‐synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non‐synonymous variations. Twenty‐four (10%) patients had non‐synonymous variations in COI , whereas 13 (6%) patients had non‐synonymous variations in COII . The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation ( CN ‐ AML ) treated with curative intent, the presence of a non‐synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease‐free survival ( DFS ) in both univariate ( DFS ; hazard ratio ( HR ) 4.4, P = 0.006) and multivariate analyses ( DFS ; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML , and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN ‐ AML should be explored further.