Characterising the cell biology of leukemic stem cells in acute myeloid leukemia.
<p>Acute Myeloid leukemia (AML) is an aggressive haematological malignancy that mainly affects the elderly. Relapse is common and is thought to be due to the presence of chemotherapy resistant leukemic stem cells (LSC). Within the CD34+ disease (>5% of the blast cells expressing CD34) ,...
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| Format: | Thesis |
| Language: | English |
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2013
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| _version_ | 1797109954574811136 |
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| author | Cornforth, TV |
| author2 | Vyas, P |
| author_facet | Vyas, P Cornforth, TV |
| author_sort | Cornforth, TV |
| collection | OXFORD |
| description | <p>Acute Myeloid leukemia (AML) is an aggressive haematological malignancy that mainly affects the elderly. Relapse is common and is thought to be due to the presence of chemotherapy resistant leukemic stem cells (LSC). Within the CD34+ disease (>5% of the blast cells expressing CD34) , two subtypes have been identified; an LMPP/GMPlike expanded type and a MPP/CMP-like expanded type, the former is the most common, accounting for around 80% of CD34+ AML. Both the GMP-like and LMPPlike expanded populations show LSC activity. To improve our understanding of the disease and gain better insight in to how to develop treatments, the molecular basis of the disease needs to be investigated. I investigated miRNAs in the GMP/LMPP-like expanded AML. miRNAs are small non-coding RNAs involved in the regulation of mRNA. In recent years miRNAs have been shown to be implicated in many different diseases. To investigate the role miRNAs play in AML, miRNA expression was profiled in leukemic and normal bone marrow. Bioinformatic analysis was then used to examine the different miRNA expression profiles between normal and leukemic marrow. Our study showed that miRNAs are dysregulated in AML. miRNAs from the miR-17-92 and its paralogous cluster miR-106b-92 were amongst the miRNAs to be found down regulated in AML As had been seen previously at an mRNA level, on an miRNA level the LSC populations more closely resembled more mature progenitor populations than HSC and MPP populations, however the LSC populations did display an aberrant stem cell-like miRNA signature.</p> |
| first_indexed | 2024-03-07T07:48:26Z |
| format | Thesis |
| id | oxford-uuid:654b2176-fd50-427e-86f2-74e928054bef |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:48:26Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:654b2176-fd50-427e-86f2-74e928054bef2023-07-03T09:48:28ZCharacterising the cell biology of leukemic stem cells in acute myeloid leukemia.Thesishttp://purl.org/coar/resource_type/c_db06uuid:654b2176-fd50-427e-86f2-74e928054befBiologyBloodLife SciencesMolecular haematologyStem cells (clinical sciences)HaematologyClinical laboratory sciencesBiology (medical sciences)EnglishOxford University Research Archive - Valet2013Cornforth, TVVyas, P<p>Acute Myeloid leukemia (AML) is an aggressive haematological malignancy that mainly affects the elderly. Relapse is common and is thought to be due to the presence of chemotherapy resistant leukemic stem cells (LSC). Within the CD34+ disease (>5% of the blast cells expressing CD34) , two subtypes have been identified; an LMPP/GMPlike expanded type and a MPP/CMP-like expanded type, the former is the most common, accounting for around 80% of CD34+ AML. Both the GMP-like and LMPPlike expanded populations show LSC activity. To improve our understanding of the disease and gain better insight in to how to develop treatments, the molecular basis of the disease needs to be investigated. I investigated miRNAs in the GMP/LMPP-like expanded AML. miRNAs are small non-coding RNAs involved in the regulation of mRNA. In recent years miRNAs have been shown to be implicated in many different diseases. To investigate the role miRNAs play in AML, miRNA expression was profiled in leukemic and normal bone marrow. Bioinformatic analysis was then used to examine the different miRNA expression profiles between normal and leukemic marrow. Our study showed that miRNAs are dysregulated in AML. miRNAs from the miR-17-92 and its paralogous cluster miR-106b-92 were amongst the miRNAs to be found down regulated in AML As had been seen previously at an mRNA level, on an miRNA level the LSC populations more closely resembled more mature progenitor populations than HSC and MPP populations, however the LSC populations did display an aberrant stem cell-like miRNA signature.</p> |
| spellingShingle | Biology Blood Life Sciences Molecular haematology Stem cells (clinical sciences) Haematology Clinical laboratory sciences Biology (medical sciences) Cornforth, TV Characterising the cell biology of leukemic stem cells in acute myeloid leukemia. |
| title | Characterising the cell biology of leukemic stem cells in acute myeloid leukemia. |
| title_full | Characterising the cell biology of leukemic stem cells in acute myeloid leukemia. |
| title_fullStr | Characterising the cell biology of leukemic stem cells in acute myeloid leukemia. |
| title_full_unstemmed | Characterising the cell biology of leukemic stem cells in acute myeloid leukemia. |
| title_short | Characterising the cell biology of leukemic stem cells in acute myeloid leukemia. |
| title_sort | characterising the cell biology of leukemic stem cells in acute myeloid leukemia |
| topic | Biology Blood Life Sciences Molecular haematology Stem cells (clinical sciences) Haematology Clinical laboratory sciences Biology (medical sciences) |
| work_keys_str_mv | AT cornforthtv characterisingthecellbiologyofleukemicstemcellsinacutemyeloidleukemia |