Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction, Molecular Genetics and Metabolism (2015), doi: 10.1016/j.ymgme.2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The opinions presented herein are those of the authors and do not reflect the positions of all participants nor the institutions they represent. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

In order the investigate mechanisms of diminished red cell production in malignancy, we assayed erythroid progenitor cell proliferative responses to erythropoietin in plasma cloth cultures of bone marrow cells from 34 cancer patients. Erythroid colony growht by marrow cells of 11 healthy donors (means of 58 CFU‐E and 19 BFU‐E derived colonies/6 × 104 cells) was similar to that in cultures of cells from patients either with (means of 44 CFU‐E and 22 BFU‐E derived colonies/6 × 104 cells) or without was normal at all erythropoietin concentrations tested, indicating that both the CFU‐E and BFU‐E retin normal erythropoietin sensitivity in vitro. CFU‐E proliferation correlated negatively (r = − 0.56; P < 0.001) with the level of hemoglobin. In contrast to marrow cell proliferative responses to erythropoeitin, serum erythropoietin levels were inappropriately reduced in all 19 patients in whom they were measured, a finding which may be important in the pathogenesis of anemia in patients with cancer.