Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

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Bin Kaderi, Mohamed Arifin,1978-Uppsala universitet,Hematologi och immunologi,Molecular Haematology (författare)

Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

BokEngelska2010

Förlag, utgivningsår, omfång ...

Uppsala :Acta Universitatis Upsaliensis,2010
77 s.
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-110371
ISBN:9789155476779
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-110371URI

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Språk:engelska
Sammanfattning på:engelska

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Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,1651-6206 ;507

Anmärkningar

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.

Ämnesord och genrebeteckningar

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
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

Biuppslag (personer, institutioner, konferenser, titlar ...)

Rosenquist, Richard Rosenquist,ProfessorUppsala universitet,Hematologi och immunologi (preses)
Mansouri, Mahmoud,Dr.Uppsala universitet,Hematologi och immunologi(Swepub:uu)maman377 (preses)
Jansson, Mattias,Dr.Uppsala universitet,Medicinsk genetik (preses)
Alexander, Denis,ProfessorDeparment of Haematology, Haemato-Oncology Laboratory, Belfast HSC Trust, Belfast University Hospital (opponent)
Uppsala universitetHematologi och immunologi (creator_code:org_t)

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