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Chronic Lymphocytic Leukemia, Advantages of Monoclones?

Viggo Jonsson, Haneef Awan, Tom Borge Johannesen and Geir E Tjonnfjord

From a basic biological point of view, genetic traits from the human genome have been selected during a long evolution in the fight for fitness. Since the susceptibility for CLL has a genotype, a theoretical question about its advantage is relevant. This is a question about mutated monoclones and whether they are an advantage to man. We suggest that the genetic capability to provide such monoclones could be explained as reminiscence from the fetal life like a “Bad for the postnates, good for the prenates” principle. Some examples are described, e.g. the fetomaternal processing of endogenous retrovirus in the production of placenta-specific transcripts of several genes in a ceasefire balance with potential infectious exogenous retrovirus. The regulation of some cytokine reactions affected lymphocytes and monocytes around the trophoblasts, which clearly has a specific clonal pattern. Feto-maternal microchimerism with longstanding implanting of clonal maternal stem cells or lymphocytes in the offspring is yet another example giving rise to later autoimmune reactions both in the mother and in the adult life of the offspring. Based on the clinical association between CLL and the other malignant hematological disorders, seen as an increased frequency of the diagnoses in affected families, a genetic linking of their susceptibility seems likely. This entity of clonal disorders may then perhaps be seen as a previous feto-maternal genetic repertoire.