Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis

doi:10.1084/jem.179.6.1789

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Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis

SD Griffiths, DT Goodhead, SJ Marsden, EG Wright, S Krajewski, JC Reed, SJ Korsmeyer and M Greaves
Leukaemia Research Fund Centre, Institute of Cancer Research, London, United Kingdom.

We have compared the sensitivity of clonogenic interleukin 7 (IL-7)- dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis- inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells.
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