@article{
author = "Hackl, Hubert and Steinleitner, Katarina and Lind, Karin and Hofer, Sybille and Tošić, Nataša and Pavlović, Sonja and Suvajdžić, Nada and Sill, Heinz and Wieser, Rotraud",
year = "2015",
abstract = "Some 50 – 80% of patients with acute myeloid leukemia (AML)
achieve a complete remission with contemporary chemotherapy protocols, yet the majority of them eventually relapse
with resistant disease: some patients no longer respond to
chemotherapy at disease recurrence; others accomplish
second and even third remissions whose decreasing duration nevertheless indicates that the pool of residual leukemic
cells, i.e. of cells that persisted during treatment with cytotoxic
drugs, increases with every round of therapy [1]. Either of
these clinical courses therefore refl ects an enhanced chemotherapy resistance of leukemic cells at relapse as compared to
the cell population at diagnosis. Molecular changes enabling
malignant cells to survive exposure to cytotoxic drugs may
already have been present in a subset of the leukemic cell
population at presentation, or may emerge during treatment
[2,3], but in any case are thought to be selected as a consequence of drug therapy, and to play a major role in therapy
resistance at relapse. Remarkably, however, even though
various types of molecular alterations may be acquired at
relapse, neither specifi c cytogenetic alterations nor functionally relevant point mutations as identifi ed by whole genome
sequencing were associated with relapse in a recurrent manner [2,3]. Certain copy number variations and known AML
associated point mutations were newly present at relapse in
small proportions of patients (usually 10%), but the latter
were lost in other patients, indicating that they are unlikely to
represent drivers of therapy resistance at disease recurrence
[4]. Th ese fi ndings could either indicate that chemotherapy
resistance at relapse is acquired through a large variety of different mechanisms, or that molecular changes of other types
than those mentioned above are of more general relevance
in this context. Indeed, an earlier study has suggested that
the expression of specifi c genes may change in a consistent
manner between diagnosis and relapse of AML [5]. However,
only a limited number of genes and mostly unpaired samples
were probed in this investigation. Th erefore, in the present
study, genes whose expression changed in a relapse-specifi c
manner were sought in a set of paired AML samples and on
a genome-wide scale. To limit the genetic heterogeneity of
the study population, only samples from patients with cytogenetically normal (CN) AML were used.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Leukemia & Lymphoma",
title = "A gene expression profile associated with relapse of cytogenetically normal acute myeloid leukemia is enriched for leukemia stem cell genes",
pages = "1128-1126",
number = "4",
volume = "56",
doi = "10.3109/10428194.2014.944523"
}
