@article{Steven M. Kornblau_Peter P. Ruvolo_Rui-Yu Wang_V. Lokesh Battula_Elizabeth J. Shpall_Vivian R. Ruvolo_Teresa McQueen_YiHua Qui_Zhihong Zeng_Sherry Pierce_Rodrigo Jacamo_Suk-Young Yoo_Phuong M. Le_Jeffrey Sun_Numsen Hail_Marina Konopleva_Michael Andreeff_2018, place={Pavia, Italy}, title={Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival}, volume={103}, url={https://haematologica.org/article/view/8451}, DOI={10.3324/haematol.2017.172429}, abstractNote={Mesenchymal stromal cells (MSC) support acute myeloid leukemia (AML) cell survival in the bone marrow (BM) microenvironment. Protein expression profiles of AML-derived MSC are unknown. Reverse phase protein array analysis was performed to compare expression of 151 proteins from AML-MSC (n=106) with MSC from healthy donors (n=71). Protein expression differed significantly between the two groups with 19 proteins over-expressed in leukemia stromal cells and 9 over-expressed in normal stromal cells. Unbiased hierarchical clustering analysis of the samples using these 28 proteins revealed three protein constellations whose variation in expression defined four MSC protein expression signatures: Class 1, Class 2, Class 3, and Class 4. These cell populations appear to have clinical relevance. Specifically, patients with Class 3 cells have longer survival and remission duration compared to other groups. Comparison of leukemia MSC at first diagnosis with those obtained at salvage (i.e. relapse/refractory) showed differential expression of 9 proteins reflecting a shift toward osteogenic differentiation. Leukemia MSC are more senescent compared to their normal counterparts, possibly due to the overexpressed p53/p21 axis as confirmed by high β-galactosidase staining. In addition, overexpression of BCL-X<sub>L</sub&gt; in leukemia MSC might give survival advantage under conditions of senescence or stress and overexpressed galectin-3 exerts profound immunosuppression. Together, our findings suggest that the identification of specific populations of MSC in AML patients may be an important determinant of therapeutic response.}, number={5}, journal={Haematologica}, author={Steven M. Kornblau and Peter P. Ruvolo and Rui-Yu Wang and V. Lokesh Battula and Elizabeth J. Shpall and Vivian R. Ruvolo and Teresa McQueen and YiHua Qui and Zhihong Zeng and Sherry Pierce and Rodrigo Jacamo and Suk-Young Yoo and Phuong M. Le and Jeffrey Sun and Numsen Hail and Marina Konopleva and Michael Andreeff}, year={2018}, month={Apr.}, pages={810-821} }