| First Author | Passaro D | Year | 2017 |
| Journal | Cancer Cell | Volume | 32 |
| Issue | 3 | Pages | 324-341.e6 |
| PubMed ID | 28870739 | Mgi Jnum | J:357901 |
| Mgi Id | MGI:5916092 | Doi | 10.1016/j.ccell.2017.08.001 |
| Citation | Passaro D, et al. (2017) Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia. Cancer Cell 32(3):324-341.e6 |
| abstractText | The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies. Moreover, induction chemotherapy failing to restore normal vasculature was associated with a poor prognosis. Inhibition of NO production reduced vascular permeability, preserved normal hematopoietic stem cell function, and improved treatment response in PDX. |
