Seminar - Stavroula Kousteni

photo of Dr. Stavroula Kousteni
November 19, 2018 - 12:00pm
Location: 
601 Fairchild

Department of Physiology and Cellular Biophysics

Columbia University

Hosts: Iva Greenwald and Carol Prives

Title: Crosstalks between bone marrow stromal and hematopoietic stem cells in myeloid malignancies

Abstract: The bone marrow stroma (or niche) has recently emerged as a critical regulator of the development of hematological myeloid malignancies acting as a permissive microenvironment required for their emergence and progression. Alterations in the bone marrow microenvironment lead to myeloproliferative neoplasms (MPN) or myelodysplastic syndromes (MDS). We have shown that a β-catenin activating mutation expressed only in osteoblasts is sufficient to induce MDS rapidly developing to AML in mice; the disease is transplantable and characterized by clonal evolution at the cytogenetic level suggesting the induction of driver mutations in HSCs. These results are clinically relevant as 38% of AML and MDS/AML patients show nuclear accumulation and increased β-catenin signaling in their osteoblasts. Conversely, MPN or AML cells provide instructive signals that alter the function of osteoblasts to promote their engraftment and proliferation in the marrow. In the case of AML, this pathway involves serotonin receptor signaling and shows that leukemia cell engraftment and proliferation depends on their ability to compromise this signaling pathway. This biological importance of this bi-directional crosstalk between dysplastic and stromal cells suggests that development of myeloid malignancies involves alterations in the bone marrow stroma that are either transforming by themselves, or provide necessary support for mutated clonal hematopoietic cells to become dominant and dysplastic. This seminar will present applications of this hypothesis and new pathways of communications between bone marrow stromal cells and MDS cells that mediate MDS induction and its transformation to AML

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