| 1. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Exploring the Genetic Landscape in Chronic Lymphocytic Leukemia Using High-Resolution Technologies
- 2013
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 54:8, s. 1583-1590
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Forskningsöversikt (refereegranskat)abstract
- During recent years, microarray-based technologies and next-generation sequencing (NGS) has have been applied in chronic lymphocytic leukemia (CLL) in order to identify novel genomic aberrations that may contribute to the pathogenesis of the disease. Even though high-resolution microarray studies have confirmed the importance of the known recurrent aberrations, i.e. del(11q), trisomy 12, del(13q) and del(17p), and have more precisely delineated the genomic borders of these aberrations, only a few novel aberrations, found at a low frequency, have been detected with these techniques. Contrary to this, the application of NGS technology of the coding genome (exome sequencing) or the entire genome (whole-genome sequencing) has unveiled a number of novel recurrent mutations in e.g. the NOTCH1, SF3B1 and BIRC3 genes. Importantly, mutations in these latter genes were reported to be associated with particularly poor outcome, similar to TP53 aberrations, and may play key roles in tumor development, treatment resistance and prognosis. In this review, we will not only summarize the latest achievements using array-based or NGS technologies, but also point to new directions for research aiming to unravel the complex genetic 'map' in CLL and its prognostic subsets.
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| 2. |
- Gunnarsson, Rebeqa, et al.
(författare)
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New insights into the pathobiology of chronic lymphocytic leukemia
- 2011
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Ingår i: Journal of Hematopathology. - : Springer Science and Business Media LLC. - 1868-9256 .- 1865-5785. ; 4:3, s. 149-163
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Forskningsöversikt (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a varying clinical outcome; however, the pathogenic mechanisms involved in disease development have remained largely unknown. In recent years, novel biomarkers, such as certain recurrent genomic alterations and the immunoglobulin heavy variable gene mutational status, have significantly improved the subdivision of the disease along with the prognostic assessment of individual patients. Advanced molecular studies have also revealed important genetic/epigenetic events and potential susceptibility loci for CLL, as well as implicating antigens in CLL development. Furthermore, the presence of monoclonal B cell lymphocytosis (MBL) has been demonstrated to precede CLL and appears to be a pre-leukemic condition. In this review, we will not only focus on recent developments made in the fields of genetics and immunogenetics in CLL, but also provide a brief overview of MBL, since we believe that advancements in these areas will have a major impact on our understanding of CLL pathobiology.
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| 3. |
- Rosenquist Brandell, Richard, et al.
(författare)
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Prognostic markers and their clinical applicability in chronic lymphocytic leukemia : where do we stand?
- 2013
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 54:11, s. 2351-2364
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Forskningsöversikt (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a clinically and biologically heterogeneous disease where the majority of patients have an indolent disease course, while others may experience a far more aggressive disease, treatment failure and poor overall survival. During the last two decades, there has been an intense search to find novel biomarkers that can predict prognosis as well as guide treatment decisions. Two of the most reliable molecular prognostic markers, both of which are offered in routine diagnostics, are the immunoglobulin heavy chain variable (IGHV) gene mutational status and fluorescence in situ hybridization (FISH) detection of prognostically relevant genomic aberrations (e.g. 11q-, 13q-, +12 and 17p-). In addition to these markers, a myriad of additional biomarkers have been postulated as potential prognosticators in CLL, on the protein (e.g. CD38, ZAP70, TCL1), the RNA (e.g. LPL, CLLU1, micro-RNAs) and the genomic (e.g. TP53, NOTCH1, SF3B1 and BIRC3 mutations) level. Efforts are now being made to test these novel markers in larger patient cohorts as well as in prospective trials, with the ultimate goal to combine the "best" markers in a "CLL prognostic index" applicable for the individual patient. Although it is clear that these studies have significantly improved our knowledge regarding both prognostication and the biology of the disease, there is still an immediate need for recognizing biomarkers that can predict therapy response, and efforts should now focus on addressing this pertinent issue. In the present article, we review the extensive literature in the field of prognostic markers in CLL, focus on the most clinically relevant markers and discuss future directions regarding biomarkers in CLL.
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