Because in vitro observations demonstrate the absence of lesions in the major apoptotic pathways, the model posits the absence of an intrinsic cell death defect in the majority of the leukemic clones. We do not rule out the possibility that developing genetic alterations in the evolving clone can tip the balance between pro- and anti- apoptotic molecules in such a way as to favor B-CLL cell survival. However, the influence of external signals appears to dominate based on current knowledge. This is in line with the in vivo labeling studies indicating the dynamic nature off CLL clones.
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