Breast cancer promotes myelopoiesis by altering hematopoietic stem cells and the bone marrow stromal niche.

Increased numbers of circulating myeloid cells are a hallmark of most cancers, however it remains unclear how primary tumors impact myelopoiesis. Here we show that non-metastatic breast tumors remotely instruct long-term hematopoietic stem cell (HSCLT) fate in the bone marrow (BM) by promoting their proliferation and differentiation into myeloid cells. As such, HSCLT from tumor-bearing mice acquire a myeloid potential that persists when HSCLT are transferred in lethally-irradiated tumor-free animals. In addition, we show that the cell-intrinsic HSCLT myeloid lineage commitment is strengthened by the concomitant modification of the stromal compartment of the BM hematopoietic niche. By imaging the niche, we found that physical interactions between mesenchymal stem cells and HSCLT are increased in situ.  Moreover, co-culture experiments show that mesenchymal stem cells isolated from the BM of tumor-bearing mice favors HSCLT myeloid differentiation in vitro. Together our data reveal that cancer remotely alters BM hematopoiesis at the earliest differentiation stage, by modulating both HSCLT and their BM stromal niche. Therefore, cancer-induced systemic changes impact on the entire BM compartment, favoring the output of myeloid cells that fuel the pool of protumorigenic cells in the tumor-bed. In this work i am a second author and contributed through the bioinformatics analysis of transcriptomics data. This work was performed in collaboration with Julie Helft and Yohan Gerber (Institut Cochin & Institut Curie, Paris).

Link to preprint (currently in press at Nature Cell Biology)