ABSTRACT
Apoptosis, a type of programmed cell death, is a genetically encoded process that is
engaged when a cell detects the existence of sufficient damage or derangement. Examples
of insults that trigger programmed cell death include oncogene activation, genomic
instability, growth factor withdrawal, DNA damage, and anoikis. Most or all cancer cells
endure many of these insults and thus need to circumvent apoptosis to survive. Chronic
lymphocytic leukemia (CLL) cells, characterized by a low rate of proliferation and
prolonged life span, are often considered to have a defect in their apoptosis pathways
rather then aberrant cell cycle progression (1,2). Therefore, CLL is often described as
malignancy of failed apoptosis (3), seemingly implying that the apoptotic pathway is broken.
However, CLL cells are very sensitive to agents that induce apoptosis (4). This observation
suggests that apoptosis signaling in CLL cells is not irreparably broken, but rather
reversibly blocked in CLL.While the molecular alterations that circumvent apoptosis can
potentially occur at many different levels, it is becoming increasingly clear that the
mitochondrion is a key place in the apoptotic pathway for these blocks to occur in CLL.
The major proteins involved in apoptotic signaling at the mitochondrion are BCL-2
family members.
