Excessive apoptosis in low risk myelodysplastic syndromes (MDS)

Citation
Je. Parker et Gj. Mufti, Excessive apoptosis in low risk myelodysplastic syndromes (MDS), LEUK LYMPH, 40(1-2), 2000, pp. 1-24
Citations number
199
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Hematology,"Onconogenesis & Cancer Research
Journal title
LEUKEMIA & LYMPHOMA
ISSN journal
1042-8194 → ACNP
Volume
40
Issue
1-2
Year of publication
2000
Pages
1 - 24
Database
ISI
SICI code
1042-8194(200012)40:1-2<1:EAILRM>2.0.ZU;2-H
Abstract
The paradox of peripheral cytopenias despite a normo/hypercellular marrow i n MDS has been ascribed to excessive intramedullary hematopoietic cell apop tosis. Programmed cell death (PCD) in early disease might be triggered by t he BM microenvironment, mediated either through inhibitory cytokines such a s tumor necrosis factor alpha (TNF-alpha) or fas/fas ligand signaling or th rough a relative deficiency in hematopoietic growth factors. Intrinsic cell ular defects giving rise to abnormalities in cell-cell or cell-stromal inte raction, cell signaling or cell cycling may also underlie hematopoietic pro genitor apoptosis. Alternatively, an early 'hit' in the multistep pathogene sis of MDS may result in a higher proliferative rate of the neoplastic clon e. Increased apoptosis may thus represent a homeostatic process to control cell numbers. This paper shall summarize current evidence implicating a rol e for increased PCD in low risk MDS, outline possible etiologic factors and suggest potential therapeutic mechanisms whereby excessive hematopoietic p rogenitor cell apoptosis might he circumvented.