Subtractive Hybridization Identifies Stem Cell-Associated Genes in an Acute Myeloid Leukemia with Poor Prognosis
- Author:
Ngiow Shin Foong
;
Maha Abdullah
;
Jasmine Lim
;
Cheong Soon-Keng
;
Seow Heng-Fong
- Publication Type:Journal Article
- Keywords:
Acute myeloid leukemia;
Gene profiling;
Subtractive hybridization;
Leukemia stem cell
- MeSH:
Leukemia, Myeloid, Acute
- From:Malaysian Journal of Medicine and Health Sciences
2016;12(1):19-31
- CountryMalaysia
- Language:English
-
Abstract:
Introduction: Current prognostic markers have improved survival prediction, however, it has not
advanced treatment strategies. Gene expression profiling may identify biological markers suitable as
therapeutic targets. Leukaemia stem cell is associated with adverse outcome, however, its biological
characteristics are still being investigated. We observed higher in vitro cell viability in acute myeloid
leukaemia (AML) samples with poor prognosis, which may be stem cell related. Objective: The
objective of this study was to profile highly expressed genes in an AML sample of poor prognosis/high
viability and compare with a sample of good prognosis/low viability. Method: Subtractive hybridization
was performed on two AML samples with high blast counts (>80%), a poor prognosis, PP (disease free
survival, DFS<12 months) and a good prognosis, GP (DFS>12 months) sample. The PP sample had
higher CD34+ counts (73% vs 46%) and higher cell viability than the GP sample. cDNA libraries were
subsequently cloned and sequenced. Results: cDNA subtracted from the PP samples was identified
as genes active during fetal/embryonic development (LCOR, CNOT1, ORMDL1), HOX- related genes
(HOXA3, PBX3, SF3B1), hematopoiesis (SELL, IL-3RA) and aerobic glycolysis/hypoxia (PGK1,
HIGD1A) -associated genes. Majority of GP clones isolated contained genes involved in oxidative
phosphorylation, OXPHOS (COXs, ATPs, MTND4 and MTRNR2), protein synthesis (including
ribosomal proteins, initiating and elongation factors), chromatin remodeling (H2AFZ, PTMA), cell
motility (MALAT1, CALM2, TMSB4X), and mitochondria (HSPA9, MPO) genes. Conclusion: Thus,
the PP sample exhibited stem cell-like features while the GP sample showed cells at a high level of cell
activity. These genes are potential prognostic markers and targets for therapy.
- Full text:P020160902386308837056.pdf
