Authors: Pessina, Augusto; Malerba, Ilaria; Gribaldo, Laura

Source: Current Pharmaceutical Design, Volume 11, Number 8, March 2005 , pp. 1055-1065(11)

Publisher: Bentham Science Publishers

Abstract:

In vitro clonogenic assays have been developed and widely used since many years to investigate the proliferation and the differentiation both of pluripotent haemopoietic stem cells (PHSC) and of the different progenitors of blood cell lineages: megakaryocytes (Colony Forming Unit-Mk) granulocyte -macrophage (CFU-GM), erythrocytes (BFU-E/CFU-E). As these techniques have been introduced, they appeared to be very useful to investigate the pathogenic mechanisms of drug induced blood disorders and also for screening compound during preclinical safety study. Because the integrity of the hematopoiesis is also essential to guarantee the immunological function, the application to the toxicology of these clonogenic assays, provides an essential tool for better understanding the in vivo observation (experimental and clinical) by also helping in predicting the degree of a possible in vivo hematotoxic in drug treated patients. The review introduces to basic concepts on hematopoiesis and on classical evaluation of a drug hematotoxic phenomenon. It describes the application of each clonogenic test to assess the specific hematotoxicity action. Moreover it report the most recent studies on standardisation, prevalidation and validation of such assays and critically reviews a model for predicting myelotoxicity by discussing the main aspects referred to the evaluation of the in vivo acute neutropenia by using the in vitro CFU-GM assay.

Keywords: clonogenic assay; hematotoxicity; myelotoxicity; bfu-e/cfu-e; cfu-gm; cfu-mk prediction model validation

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612053381648

Affiliations: 1: Augusto Pessina, Institute of Microbiology, Via Pascal 36, 20133, Milan, Italy.

Publication date: 2005-03-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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