Porto, G. | Search bioRxiv

bioRxiv2020

Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in AML patients at diagnosis and mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile not associated with inflammation or transfusion and characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that leukemic blasts take up iron and that the AML-induced loss of erythroblasts is responsible for iron redistribution and an increase in TSAT. We also show that elevated TSAT at diagnosis is independently associated with increased overall survival in AML and suggest that TSAT may be a relevant prognostic marker in AML.

cancer biology↗

bioRxiv2020

Cooperative efforts on developing vaccines and therapies for COVID-19

Health organizations have always sought partnership to join competencies in innovation, even with fierce competition in this sector. In this pandemic moment it is relevant to observe how organizations behave to seek quick and safe answers. The present research analyzes how the cooperation networks were set off considering the clinical trials on therapies and vaccines that were developed specifically to treat or prevent COVID-19. Social Network Analysis technique was used to build cooperation networks and apply metrics that characterize these connections. There was an evaluation of statistics of Strength of cooperation and Unilateral dependence of cooperation that identify the cooperation strength between two organizations, and the dependence of this relations. A total of 415 clinical trial were identified, of which 42% are in cooperation. From organizations that have partnership, firms are the first, followed by universities. We extracted the main categories that concentrate 74% of partnerships in the trials of antibody, and vaccine. Several organizations cooperate in multiple categories of trials, evidencing the efforts to focus on different strategies to treat the disease. We found high strength of cooperation and an assimetryc dependency between partners, which can be assigned to specialized models of partnership and it occurs in competitive enviroments like this pandemic moment. Cooperation were not limited to geographical proximity and the advent of Chinese players can represent a new change in the biotechnological development axis. Finally, the challenge of finding therapeutic or immunological solutions for COVID-19 demonstrates a clear composition of cooperation groups that complement their skills to manage organizational strategies to beat the pandemic. In this new paradigm, there can be partnerships not only in clinical trial but also in pre-competitive technologies development. This experience is expected to change the way of organizations define their R&D strategies and start to adopt more a collaborative innovation model.

scientific communication and education↗