Fig. 1

Model integrating the infectious etiology hypothesis with the potential role of Th cells in BCP-ALL pathogenesis. Precursor B cells develop in the bone marrow, where they may undergo chromosomal rearrangements. Cells harboring such translocations that confer survival advantages are often present as expanded clones at birth, but this does not necessarily lead to leukemia development (left side). Infections in early childhood induce expansion of Th cells, which home to the bone marrow after the infection has been cleared to take part in normal hematopoiesis and to rise a memory response upon re-challenge with the pathogen (left side). Th cells expanded during an aberrant immune response due to delayed pathogen exposure may aberrantly interact with precursor B cells or leukemia cells or both after migration to the bone marrow, supporting their growth and survival, which ultimately leads to leukemia (right side)