Here, we identify gp130-STAT1/3 as a vital pathway in leucopoiesis, whereas gp130-Ras controls early thrombopoiesis after BMT. BMT is a clinically well-established procedure for decades. However, a detailed understanding of underlying molecular processes involved in stem cell engraftment and proliferation is still incomplete. IL-6 is an important cytokine that not only regulates the homeostasis of haematopoietic stem cells but that is prominently involved in the control of various inflammatory processes. The latter is important especially for BMT, which naturally comprises the need for immunosuppression, thereby provoking many clinically relevant infectious and inflammatory conditions. Moreover, patients who finally undergo BMT have usually been treated before with several bone marrow injuring chemotherapeutic drugs. Due to the toxic nature of most used therapeutics not only the stem cell pool, but also the microenvironment including endothelial and supporting stromal cells in recipient’s BM is affected. Thus, subsequently infused donor cells do not only have to combat with immunological challenges but also with the situation of an inflamed and structurally disintegrated stem cells niche. Interestingly, the regulatory interleukin-6 pathway also seems to play an important role during those pre-conditioning processes and is therefore of particular relevance. In contrast, we observed a strong dependency on gp130-signals within the transplanted BM cells. Mice receiving gp130-depleted BM showed transient leukopenia, anaemia and thrombocytopenia and a severely compromised survival if low cell numbers were transferred. Thus, gp130- dependent signalling in donor cells seems to affect all BM lineages. This is an important and novel observation because it demonstrates that gp130-dependent gene activation is required for proper expansion of blood progenitor cell lineage. Notably, 6 weeks after irradiation and transplantation most lineages were able to recover, which may be best explained by compensatory mechanisms such as extramedullary haematopoiesis. Importantly, we did not observe a preferential selection of potentially remaining non-gp130-deleted cells in the BM of recipient mice. This could reflect that gp130 is most important for proliferation of the rather immature BM progenitors. Moreover, very likely there is a threshold effect of gp130, because otherwise the transplantation of gp130-deficient BM would have even more severe effects on survival. The second indication for dose-dependency stems from our experiment using limited amounts of donor cells. Here, recipient mice ultimately died only if the number of transplanted cells was reduced below a certain threshold of approximately 16105 cells. Under real life clinical conditions treatment of neoplasms – not only hematopoietic neoplasms – and BM-failure comprises the homeostasis of the whole organism. Both, the disease itself and the used treatments provoke a) a local and b) an often even systemic inflammatory environment within the affected patient that is BI-D1870 501437-28-1 mediated by cytokines or growth factors.