Puppet masters of B-cell progenitor acute lymphoblasticleukemia: The preB cell receptor and the interleukin 7 receptor α

B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) is enriched for a preB cell phe-notype, hinting at a specific vulnerability of this cell stage. Two signaling pathways viathe preB cell receptor (preBCR) and the interleukin 7 receptorα(IL-7Rα) chain govern thebalance between differentiation and proliferation at this stage and both receptor path-ways are routinely altered in human BCP-ALL. Here, we review the immunobiology ofboth the preBCR as well as the IL-7Rαand analyze the human BCP-ALL spectrum in thelight of these signaling complexes. Finally, we present a terminology for preBCR signalingmodules that distinguishes a pro-proliferative “phase-I” module from a pro-differentiative“phase-II” module. This terminology might serve as a framework to better address sharedoncogenic mechanics of preB cell stage BCP-ALL.