Chronic lymphocytic leukemia: molecular genetics and animal models.
Chronic lymphocytic leukemia accounts for almost 30% of all adult leukemia cases in the United States and Western Europe. Although several common genomic abnormalities in CLL have been identified, mutational and functional analysis of corresponding genes so far have not proved their involvement in CLL. Our latest studies demonstrated functional involvement of Tcl1 oncoprotein and microRNA genes in the pathogenesis of CLL. Deregulated expression of Tcl1 in transgenic mice resulted in CLL. These CLL tumors showed abnormalities in expression of murine microRNA genes mmu-mir-15a and mmu-mir-16-1. Interestingly, human homologs of these genes, mir-15a and mir-16-1, located at the chromosome 13q14 are also deleted in human CLL samples. In this review we summarize and discuss these new developments. These recently emerged insights into the molecular mechanisms of CLL will allow for the development of new approaches to treat this disease.
Pekarsky
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Comprehensive Cancer Center, Ohio State University, Columbus 43210, USA.
Calin
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Aqeilan
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D000818:Animals; D002869:Chromosome Aberrations; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D008967:Molecular Biology; D051058:Oncogene Protein v-akt / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015398:Signal Transduction
D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; C090851:TCL1A protein, human; C490393:Tcl1 protein, mouse; D051058:Oncogene Protein v-akt