Are growth factors leukemogenic?

The National Cancer Institute (NCI) recently alerted clinicians to the possibility that patients, entered on a NCI-sponsored cooperative group trial of doxorubicin and cyclophosphamide adjuvant therapy for breast cancer, may be at high risk of developing secondary acute myeloid leukemia (AML). Secondary AML following standard doses of doxorubicin and cyclophosphamide is uncommon, suggesting that the high risk on this trial may result from its higher-than-standard doses of chemotherapy. However, the cases of secondary AML were characteristic of the type that follows treatment with topoisomerase II-active agents, especially etoposide, and this type of secondary AML is rare after treatment with either cyclophosphamide or doxorubicin at any dose. We raise the possibility that another component of this trial, hematopoietic growth factors to decrease the toxicities related to myelosuppression, may play an important role in the development of secondary AML. Growth factors not only stimulate hematopoietic progenitor proliferation and differentiation, they also regulate hematopoietic cell survival by interfering with apoptosis (programmed cell death). Inhibition of apoptosis by a variety of genetic factors is an important mechanism of oncogenesis, and appears to be the initiating event in some malignancies. Growth factor-mediated suppression of the apoptotic death of hematopoietic progenitors damaged by chemotherapy may contribute to their leukemic transformation.