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Sökning: onr:"swepub:oai:DiVA.org:uu-110371" > Assessment of Novel...

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

Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

  • E-bokAvhandlingEngelska2010

Förlag, utgivningsår, omfång ...

  • Uppsala :Acta Universitatis Upsaliensis,2010
  • 77s.

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-110371
  • ISBN:978-91-554-7677-9
  • urn:nbn:se:uu:diva-110371urn

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Klassifikation

  • Ämneskategori:vet swepub-contenttype
  • Ämneskategori:dok swepub-publicationtype
  • Ämneskategori:vet swepub-contenttype

Serie

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

Anmärkningar

  • Published
  • 1
  • <p>The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted<sup> </sup>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 <em>GNAS1</em>, <em>BCL2</em> and <em>MDM2</em> genes and the RNA expression levels of the <em>LPL</em>, <em>ZAP70</em>, <em>TCL1, CLLU1 </em>and <em>MCL1</em> genes were suggested as novel prognostic markers in CLL.</p> <p>In papers I-III, we performed genotyping analyses of the <em>GNAS1</em> T393C, <em>BCL2</em> -938C&gt;A and <em>MDM2</em> 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.</p> <p>In paper IV, we measured the RNA expression levels of <em>LPL</em>, <em>ZAP70</em>, <em>TCL1,</em> <em>CLLU1</em> and <em>MCL1</em> in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except <em>MCL1</em>, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for <em>LPL</em> and <em>CLLU1</em> expression. Among the RNA-based markers, multivariate analysis revealed <em>LPL</em> 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 <em>LPL</em> expression status giving the most significant results.</p> <p>In summary, data from papers I-III could not verify the <em>GNAS1</em> T393C, <em>BCL2</em> -938C&gt;A and <em>MDM2 </em>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 <em>LPL</em> expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize <em>LPL</em> quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.<em></em></p>

Ämnesord och genrebeteckningar

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

  • Rosenquist, Richard Rosenquist,Professor,Uppsala universitet, Hematologi och immunologi(SwePub:) (preses)
  • Mansouri, Mahmoud,Dr.,Uppsala universitet, Hematologi och immunologi(SwePub:uu) (preses)
  • Jansson, Mattias,Dr.,Uppsala universitet, Medicinsk genetik(SwePub:) (preses)
  • Alexander, Denis,Professor,Deparment of Haematology, Haemato-Oncology Laboratory, Belfast HSC Trust, Belfast University Hospital(SwePub:) (opponent)

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