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Assessment of Novel...
Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia
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- Bin Kaderi, Mohamed Arifin, 1978- (author)
- Uppsala universitet,Hematologi och immunologi,Molecular Haematology
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- Rosenquist, Richard Rosenquist, Professor (thesis advisor)
- Uppsala universitet,Hematologi och immunologi
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- Mansouri, Mahmoud, Dr. (thesis advisor)
- Uppsala universitet,Hematologi och immunologi
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- Jansson, Mattias, Dr. (thesis advisor)
- Uppsala universitet,Medicinsk genetik
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- Alexander, Denis, Professor (opponent)
- Deparment of Haematology, Haemato-Oncology Laboratory, Belfast HSC Trust, Belfast University Hospital
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(creator_code:org_t)
- ISBN 9789155476779
- Uppsala : Acta Universitatis Upsaliensis, 2010
- English 77 s.
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Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 507
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Abstract
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- The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the GNAS1, BCL2 and MDM2 genes and the RNA expression levels of the LPL, ZAP70, TCL1, CLLU1 and MCL1 genes were suggested as novel prognostic markers in CLL. In papers I-III, we performed genotyping analyses of the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL. In paper IV, we measured the RNA expression levels of LPL, ZAP70, TCL1, CLLU1 and MCL1 in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except MCL1, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for LPL and CLLU1 expression. Among the RNA-based markers, multivariate analysis revealed LPL expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results. In summary, data from papers I-III could not verify the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that LPL expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize LPL quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- chronic lymphocytic leukemia
- prognostic markers
- single nucleotide polymorphisms
- RNA-based markers
- Medical genetics
- Medicinsk genetik
- Genetics
- Genetik
- Clinical genetics
- Klinisk genetik
- Medical laboratory science
- Medicinsk laboratorievetenskap
- Oncology
- Onkologi
- Haematology
- Hematologi
- Clinical Genetics
- Klinisk genetik
- Molekylär medicin
- Molecular Medicine
- Oncology
- Onkologi
- Medicin
- Medicine
- Medical Genetics
- Medicinsk genetik
Publication and Content Type
- vet (subject category)
- dok (subject category)
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