Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis
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 ch...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
2016
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/35214/1/FKUSK1_ARTICLE_4.pdf |
| _version_ | 1825948602437992448 |
|---|---|
| author | Ngiow, Shin Foong Abdullah, Maha Lim, Jasmine Cheong, Soon Keng Seow, Heng Fong |
| author_facet | Ngiow, Shin Foong Abdullah, Maha Lim, Jasmine Cheong, Soon Keng Seow, Heng Fong |
| author_sort | Ngiow, Shin Foong |
| collection | UPM |
| description | 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 lycolysis/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. |
| first_indexed | 2024-03-06T08:31:39Z |
| format | Article |
| id | upm.eprints-35214 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T08:31:39Z |
| publishDate | 2016 |
| publisher | Faculty of Medicine and Health Sciences, Universiti Putra Malaysia |
| record_format | dspace |
| spelling | upm.eprints-352142016-10-12T04:20:42Z http://psasir.upm.edu.my/id/eprint/35214/ Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis Ngiow, Shin Foong Abdullah, Maha Lim, Jasmine Cheong, Soon Keng Seow, Heng Fong 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 lycolysis/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. Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/35214/1/FKUSK1_ARTICLE_4.pdf Ngiow, Shin Foong and Abdullah, Maha and Lim, Jasmine and Cheong, Soon Keng and Seow, Heng Fong (2016) Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis. Malaysian Journal of Medicine and Health Sciences, 12 (1). pp. 19-31. ISSN 1675-8544 http://www.medic.upm.edu.my/dokumen/FKUSK1_ARTICLE_4.pdf |
| spellingShingle | Ngiow, Shin Foong Abdullah, Maha Lim, Jasmine Cheong, Soon Keng Seow, Heng Fong Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis |
| title | Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis |
| title_full | Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis |
| title_fullStr | Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis |
| title_full_unstemmed | Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis |
| title_short | Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis |
| title_sort | subtractive hybridization identifies stem cell associated genes in an acute myeloid leukemia with poor prognosis |
| url | http://psasir.upm.edu.my/id/eprint/35214/1/FKUSK1_ARTICLE_4.pdf |
| work_keys_str_mv | AT ngiowshinfoong subtractivehybridizationidentifiesstemcellassociatedgenesinanacutemyeloidleukemiawithpoorprognosis AT abdullahmaha subtractivehybridizationidentifiesstemcellassociatedgenesinanacutemyeloidleukemiawithpoorprognosis AT limjasmine subtractivehybridizationidentifiesstemcellassociatedgenesinanacutemyeloidleukemiawithpoorprognosis AT cheongsoonkeng subtractivehybridizationidentifiesstemcellassociatedgenesinanacutemyeloidleukemiawithpoorprognosis AT seowhengfong subtractivehybridizationidentifiesstemcellassociatedgenesinanacutemyeloidleukemiawithpoorprognosis |