title: The clinical significance of caspase regulation in acute leukemia.
abstract: Disruptions of pathways of programmed cell death, or apoptosis, are increasingly found in malignant cells of both solid and hematologic neoplasms. Caspases belong to a family of cysteine proteases and have emerged as central regulators of the apoptotic cascade. Despite many and diverse signals that can trigger apoptosis, the execution of apoptosis appears to be uniformly mediated through activation of caspase enzymes. Inapproriate expression of caspases or malfunctions in their regulation through other pathways may also be an important step in the pathogenesis of acute leukemias. Recent studies have shown that overexpression of the inactive forms of caspases CPP32 (caspase 3) and ICH-1 (caspase 2) is frequently observed in the blasts of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Many other enzymes involved in apoptosis are expressed at high levels in patients with acute leukemia. Whether this signals the capacity of leukemic cells to rapid induction of apoptosis with fast reduction of the burden of disease and favorable clinical outcome, or accumulation of inactive substrates that cannot be activated by lack of cellular mechanisms to do so, requires further investigation. With the identification of many other regulators of apoptotic activity in the leukemic cells, new targets for future therapy may be identified and many new insights can be gained in understanding the biological behavior of response and resistance to therapy as well as control and relapse from minimal residual disease.
authors: Department of Leukemia and Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors: S
authors: S
authors: Faderl
authors: Z
authors: Z
authors: Estrov
mesh_terms: D000208:Acute Disease; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D020169:Caspases