Chronic Myeloid Leukemia Incidence Based Estimates of Hematopoietic Stem Cell Numbers per Person

Discussion: It is not known why CML incidence is lower in Nagasaki. Environmental exposures in Nagasaki not present in Hiroshima may have lowered N within the HSC dead-band, either via direct HSC killing or via HSC exhaustion as a result of high downstream cell turnover. For HSC killing as the mechanism, as most HSC are quiescent and thus in G0/G1 wherein error-prone non-homologous end-joining DNA double strand break repair is dominant, suspects include agents that cause cell-lethal DNA double-strand break misrejoinings, such as large deletions and dicentrics. Nagasaki survivors had greater gamma vs. neutron exposures due to plutonium vs. uranium bomb differences, and for a fixed dose, this decreases the probability of killing a struck HSC while increasing the probability of an HSC being struck. Neutron doses were, however, a small fraction of total doses. Another option is a chemical exposure. Chemotherapy reducing radiation-induced CML in Figure 1 suggests that differences in city industries should be considered. For HSC exhaustion as a mechanism of lowering N, if pregnancies reduce breast cancer risks by consuming target cells, a chronic infection could in principle also shift N down in the dead-band. HTLV in Nagasaki but not Hiroshima is not suspected, but perhaps it should be. Radiation does not induce adult T-cell leukemia (ATL), but HTLV lowering N in most people infected might be independent of it causing ATL in a few, and N stopping at the dead-band threshold implies...
Source: Blood - Category: Hematology Authors: Tags: 632. Chronic Myeloid Leukemia: Therapy Source Type: research