Prediction of potential drug myelotoxicity by in vitro assay on hematopoietic progenitors

Clonogenic assays have been developed and used to investigate the proliferation and the differentiation in vitro both of pluripotent hemopoietic stem cells and of the different progenitors of blood cell lineages. Their application to the toxicology provides an essential tool to better understand the "in vivo" observation (experimental and clinical) by also helping the prediction of the degree of a possible " in vivo" myelotoxicity in drug treated patients. A standard procedure developed and validated to determine the in vitro myelotoxic effect of drugs and chemicals both towards murine and human progenitors is described here. An algorithm is also suggested to be applied by using the " in vitro CFU-GM assay“ for predicting the Maximal Tolerated Dose (MTD) to enter phase I clinical study. A miniaturized procedure in 96-wells plate may be also used to high-throughput screening of compounds or if very small amounts are available.