From the early 1900s, it has been known that ionizing radiation (IR) impairs hematopoiesis through a variety of mechanisms. IR exposure directly damages hematopoietic stem cells and alters the capacity of bone marrow stromal elements to support and/or maintain hematopoiesis in vivo and in vitro. Exposure to IR induces dose-dependent declines in circulating hematopoietic cells not only through reduced bone marrow production, but also by redistribution and apoptosis of mature formed elements of the blood. Recently, the importance of using lymphocyte depletion kinetics to provide a “crude” dose estimate has been emphasized, particularly in rapid assessment of large numbers of individuals who may be exposed to IR through acts of terrorism or by accident. A practical strategy to estimate radiation dose and triage victims based upon clinical symptomatology is presented. An explosion of knowledge has occurred regarding molecular and cellular pathways that trigger and mediate hematologic responses to IR. In addition to damaging DNA, IR alters gene expression and transcription, and interferes with intracellular and intercellular signaling pathways. The clinical expression of these disturbances may be the development of leukemia, the most significant hematologic complication of IR exposure among survivors of the atomic bomb detonations over Japan. Those at greatest risk for leukemia are individuals exposed during childhood. The association of leukemia with chronic, low-dose-rate exposure from nuclear power plant accidents and/or nuclear device testing has been more difficult to establish, due in part to lack of precision and sensitivity of methods to assess doses that approach background radiation dose. Nevertheless, multiple myeloma may be associated with chronic exposure, particularly in those exposed at older ages.
