XIII Congress of the Italian Society of Experimental Hematology Rimini, Italy, October 15–17, 2014

摘要

Mesenchymal stromal cells (MSCs) are multipotent non-hematopoiet- ic stem cell precursors residing virtually in all pre-natal and adult tissues, including bone marrow (BM), and capable of self-renewal and differen- tiation into a number of mesodermal cell lineages (fibroblasts, osteoblasts, adipocytes, and chondrocytes). MSCs display a homogeneous mesenchy- mal immunophenotype (i.e. CD105, CD44, CD73, CD90, CD146 mark- er expression) and acquire, once activated by inflammatory cytokines (licensing), a strong and broad modulatory effect towards all the effector cells of both innate and adaptive immunity, a property that is shared also by the fibroblastic progeny. MSCs are essential components of the BM microenvironment regulating and supporting the survival, proliferation and differentiation of normal hematopoietic stem cells and progenitors, as well as the development of different tumors, including hematological malignancies. Senescence or genotypic abnormalities of BM-MSCs may determine phenotypic alterations of hematopoietic stem cells and progen- itors that may eventually lead, if additional genotypic abnormalities occur, to the onset of myelodisplasia and leukemic transformation. In addition, inflammatory licensing of the mesenchymal progenitors may eventually contribute to tumor development by favouring the onset of a ‘immunolog- ical sanctuary’that prevents tumor cells from being eliminated by immune effector cells. Different molecular pathways are involved in stromal cell supportive functions towards cancer cells; among them, Notch signalling plays a significant role in the reciprocal interactions between stromal microenvironment and neoplastic cells of hematological origin, such as ALL, CLL and AML cells, by promoting cell survival and resistance to chemotherapy. Therefore, targeting Notch pathway activation may rep- resent a useful strategy to overcome drug resistance and improve the effi- cacy of conventional treatments.