Exploiting biological diversity and genomic aberrations in chronic lymphocytic leukemia

Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
Leukemia & lymphoma (Impact Factor: 2.89). 12/2011; 53(6):1023-31. DOI: 10.3109/10428194.2011.631638
Source: PubMed


There is remarkable heterogeneity in the clinical course and biological characteristics of patient subgroups with chronic lymphocytic leukemia (CLL). Mutations of key tumor suppressors (ATM, miR-15a/16-1 and TP53) have been identified in CLL, and these aberrations are important "drivers" of the disease and some of its clinical characteristics. While some mutations are associated with poor outcome [particularly del(17p) and TP53 mutation], others are linked to a favorable clinical course [e.g. del(13q) as sole aberration]. In addition to genetic aberrations, antigen drive and microenvironmental interactions contribute to the pathogenesis of CLL. How the genetic aberrations impact on the process of antigen drive or microenvironmental interactions is currently unclear. Our improved understanding of the biology and clinical course of specific genetic subgroups is beginning to be translated into more specific and targeted treatment approaches. As a result, genetic subgroups are treated in distinct protocols. This review summarizes the contribution of the microenvironment and the most important genetic aberrations in CLL and how our improved knowledge of the biology of CLL may translate into improved treatment results.

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    • "s carrying a del ( 11q ) clone display inactivating mutations of the second ATM allele and these cases show a poor chemotherapy response , reminiscent of what has been described for TP53 - defective CLLs ( Austen et al . , 2007 ) . In addition , patients carrying a del ( 11q ) clone typically show rapid progression , and reduced overall survival ( Seiffert et al . , 2012 ) . As for TP53 , disabling ATM mutations are enriched in chemotherapy - treated patients , again suggesting that an inactivation of the pro - apoptotic DDR is selected for in CLL ( Puente et al . , 2011 ; Quesada et al . , 2011 ) . It remains to be seen whether the novel agents , including ibrutinib , idelalisib , ABT - 199 , obinotuzu"
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    • "Expression of antigens was analyzed for fluorescence using a Particle Analyzing System (PAS) flow cytometer (Partec, Germany). The positive expression of CD38 in the test cell population was the presence of the antigen on at least 10 % of the cells [18]. "
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