Infection causes childhood leukemia

accounts for a third of all cancers in children under the age of 15, mostly affecting industrialized countries, being the B-precursor acute lymphoblastic leukemia (pB-ALL) the most common type. The disease commonly strikes young children at the age of two to five years, and is treated with aggressive chemotherapy. In recent decades, more effective treatments have boosted survival rates and reduced mortality for childhood leukemia. However, according to SEER data from the National Cancer Institute, the incidence of lymphoblastic leukemia (ALL) in 0-14 year-old US children increased from 2.2 per 100,000 in 1975 to 4.0 per 100,000 in 2005. This might be caused in part due to better cancer registries but there is little doubt that the real incidence of this " modern lifestyle " malignancy also rose. Hence, preventive strategies are clearly superior to any therapy improvement. Environmental exposures came into the focus of many epidemiologists who initiated a number of well-conducted studies aiming to elucidate the etiological role of infection, nuclear power-plants, background terrestrial irradiation and many other putative factors. Over the past century, infections have been regarded as the most likely cause of childhood leukemias [1]. But in general, epidemiological studies are descriptive and sometimes vary in their main conclusions. Similarly, when wild type mice were born and kept in the specific-pathogen-free (SPF) environment until moved to common infectious environment they do not to develop pB-ALL [2]. These results suggest that delayed-exposure to infection is not involved in the leukemia etiology. However, it is potentially possible that, in humans, infection-exposure favors pB-ALL in children harboring an intrinsic genetic susceptibility. Recently, germline mutations in PAX5 have been described as conferring an inherited risk for pB-ALL and pB-ALL occurs in affected children at reduced penetrance [3, 4]. To elucidate if pB-ALL is a result of infection exposure, Pax5+/-mice were exposed to common pathogens after being born in SPF condition. Pax5+/-mice developed clonal pB-ALL recapitulating the clinical, histopathological and molecular features of human pB-ALL. These data represent the first proof that delayed exposure to infection can induce human-like pB-ALL in mice on the basis of inherited genetic predisposition, suggesting that a similar scenario may occur in human Editorial pB-ALL [2]. The demonstration that pB-ALL development can be established in mice by delayed exposure to infection implies that either abolishing infection or exposure to infection very early after birth will interfere with pB-ALL generation (Figure 1). In agreement with this, Pax5+/-mice …