Molecular pathogenesis and targets for therapy in myelodysplastic syndrome (MDS) and MDS-related leukemias

Research output: Contribution to journalReview article

Abstract

The myelodysplastic syndromes (MDS) are a family of disorders that are characterized by ineffective hematopoiesis and evolution to acute myelogenous leukemias (AMLs) that are strikingly refractory to current therapeutic approaches. A substantial proportion of these complex diseases arise in the setting of exposures to environmental or occupational toxins, including cytotoxic therapy for a prior malignancy or other disorder (secondary MDS/AML). On the genomic level, MDS is typified by losses and translocations involving certain key gene segments, with disruption of the normal structure and function of genes that control the balance of proliferation and differentiation in hematopoietic precursors. In addition, MDS cells display impaired responses to diverse cytokines in terms of activating signaling intermediaries that trigger both proliferation and differentiation, and the disruption of the normal flow of biochemical information along the pathways translates into ineffective multilineage hematopoiesis and bone marrow failure. MDS/AMLs provide a fertile testing ground for the development of novel agents and the concomitant molecular dissection of the mechanisms by which these agents induce growth inhibition, terminal differentiation, and eventual cell death.

Original languageEnglish (US)
Pages (from-to)3-9
Number of pages7
JournalCurrent opinion in oncology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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