Apoptosis in blood diseases. Review new data.
In this report we reviewed the recent data regarding the involvement of apoptosis or programmed cell death in hematological diseases. We summarized new features of apoptosis including high molecular weight DNA fragmentation and programmed cell death of enucleated cells. We described the recent contributions about the three oncogenes bcl-2, p53 and c-myc. New inducers and inhibitors of apoptosis have been reported, particularly the role of stromal environment, thrombopoietin, erythropoïetin and flt-3 ligand has been mentioned. Apoptosis has been studied in red cell pathology: polycythemia, thalassemia and deficiency in folates, vitamin B12, iron and G6PD. Recently, the involvement of programmed cell death has been documented in bone marrow failure and myelodysplasia. In Acute Leukemia, the therapeutic action of numerous drugs has been proven by their in vitro apoptotic effect. The resistance of malignant cells to apoptosis, in Chronic Myeloïd Leukemia, due to bcr-abl oncogene, has been partially explained by conformational changes in p53 expression and is reversed by retinoic acid. Numerous reports in Chronic Lymphocytic Leukemia have documented the major role of apoptosis in this disease, especially in therapeutic efficacy of Chlorambucil, Fludarabine and Methylxanthine derivatives. At least, in Myeloma, it has been shown that apoptosis is induced by dexamethasone and HMBA, and inhibited by interleukine 6 that prevents activation of SAP Kinases.
Binet
J L
JL
Department of Hematology, Hôpital Pitié-Salpétrière, Paris, France.
Mentz
F
F
Merle-Beral
H
H
D000818:Animals; D017209:Apoptosis; D006402:Hematologic Diseases / Q000473:pathology*; D006801:Humans