Candidate drugs and other compounds can be toxic to the sensitive cells of the bone marrow, primarily the blood-forming progenitor cells. The typical physiological consequence of bone marrow toxicity (hemotoxicity or hematotoxicity) is myelosuppression.
Myelosuppression (also known as bone marrow suppression) is a condition where the bone marrow has been adversely affected, resulting in lowered blood cell numbers. Chemotherapies and other therapeutic agents, toxic substances and immune modulating agents often cause one or more types of myelosuppression by affecting the viability, profileration or differentiation potential of the progenitors of the various blood cell lineages. Any or all lineages of blood cells may be affected. Neutropenia results when an agent is toxic to the myeloid progenitors, while severe anemia is caused by toxicity of the erythroid (red blood cell) progenitors and thrombocytopenia is the result of toxicity to the progenitors of the megakaryocytic (platelet) lineage. Whether these effects are direct or indirect, ReachBio’s scientists are experts at evaluating them using powerful functional in vitro Colony Forming Cell (CFC) or Colony Forming Unit (CFU) assays. These assays utilize normal bone marrow stem cells and progenitor cells from human, mice, rats and other species, making them both relevant and predictive. Click here to see an example of how the results from our in vitro hemotoxicity assays correlate with clinical myelosuppression.
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Types of Hemotoxicity (Myelosuppression) and Related Assays:
Neutropenia & Myeloid Toxicity (CFU-GM, CFU-G)
Neutropenia is a hematological condition that is characterized by abnormally low numbers of neutrophils in the blood.
Clinical neutropenia is often caused by toxicity of a substance (e.g. drug or toxic agent) to the myeloid progenitors resident in the bone marrow. The number and functionality of myeloid progenitors can be accurately evaluated in the CFU-GM assay, an in vitro Colony Forming Cell (CFC) assay. This makes the CFU-GM assay an excellent model for assessing the myelotoxic potential of new clinical compounds and predicting the level of clinical neutropenia they may cause. The sensitivity of CFU-GM assays often produces results with such a high correlation to observed clinical neutropenia that this assay can even be used to rank each compound within a tested series for the level of clinical neutropenia they are likely to cause if given to patients.
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Thrombocytopenia & Megakaryocyte Toxicity (CFU-Mk)
Thrombocytopenia is characterized by any disorder where there is an abnormally low number of platelets in peripheral blood.
Clinical thrombocytopenia is often caused by substances (e.g. drug or toxic agent) that are toxic to the resident megakaryocyte progenitors in the bone marrow. The number and functionality of megakaryocyte progenitors can be accurately evaluated in the CFU-Mk assay, an in vitro Colony Forming Cell (CFC) assay. This makes the CFU-Mk assay an excellent in vitro model for evaluating new drug candidates for their potential to cause thrombocytopenia in the clinic.
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Anemia is a condition in which there is an abnormally low number of red blood cells in the blood.
Clinical anemia is often caused by substances (e.g. drugs or toxic agents) that are toxic to the erythroid progenitors resident in the bone marrow.The number and functionality of erythroid progenitors can be accurately evaluated in the BFU-E assay. This makes the BFU-E assay an excellent in vitro model for evaluating new drug candidates for their erythrotoxic potential and for predicting the likelihood that the compounds would cause clinical anemia if given to patients.
CONTACT US to learn about our in vitro BFU-E hemotoxicity assay services to predict and evaluate drug-induced anemia and erythroid progenitor toxicity.