Apoptosis: molecular regulation of cell death and hematologic malignancies

We describe the molecular mechanisms of apoptosis and its relationships with hematologic malignancies, stressing the concept that, both positive and negative deregulation of apoptosis, may be involved in hematologic human diseases. So, this fundamental process must be balanced by so far unknown mechanisms, involving caspases (cysteine proteases, cleaving the protein substrate after an aspartate residue). These, so far known, ten proteases, are interconnected in a molecular cascade, initiated by the release of cytochrome C from mitochondrial membranes and its interaction with APAF-1 (the homolog of the Caenorhabditis e. CED-4) and with caspase 9, that initiates the proteolitic cascade (1,2). The conclusion is that apoptosis is a very important process, but yet poorly known in molecular details, in spite of the efforts of many scientists. Even the role of bcl-2, the main gene protecting from apoptosis, is still unknown. We close this chapter with a list of ten different technical approaches that can be useful tools to study apoptosis, and tracing the molecular principles on which they are based.