Abstract
Successful hematopoietic stem cell transplantation (HSCT) involves the restoration of hematopoietic function after engraftment, arising from the differentiation and proliferation of hematopoietic stem cells. Several factors could influence the course of allogeneic-HSCT (allo-HSCT). Therefore, knowledge of serum proteome changes during the allo-HSCT period might increase the efficacy of diagnosis and disease prevention efforts. This study conducted proteomic analyses to find proteins that were significantly altered in response to allo-HSCT. Sera from five representative patients who underwent allo-HSCT were analyzed by 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry, and were measured on a weekly basis before and after allo-HSCT in additional 78 patients. Fourteen protein spots showing changes in expression were further examined, and most proteins were identified as acute phase proteins (APPs). Studies of 78 additional patients confirmed that C-reactive protein (CRP) and haptoglobin undergo expression changes during allo-HSCT and thus may have the potential to serve as representative markers of clinical events after allo-HSCT. Maximal CRP level affected the development of major transplant-related complications (MTCs) and other problems such as fever of unknown origin. Particularly, an increase in CRP level 21 days after allo-HSCT was found to be an independent risk factor for MTC. Maximal haptoglobin and haptoglobin level 14 days after allo-HSCT were predictive of relapses in underlying hematologic disease. Our results indicated that CRP and haptoglobin were significantly expressed during allo-HSCT, and suggest that their level can be monitored after allo-HSCT to assess the risks of early transplant-related complications and relapse.
Highlights
Successful hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation involves the transplantation of new, functional immune systems after chemotherapy and radiotherapy
When patients experience bone marrow failure or hematological malignancy, treatment generally involves chemotherapy or radiotherapy followed by the transplantation of a new and functional immune system
Allo-HSCT has dramatically improved patient survival rate, the broader applications of this therapy remain limited because of the life-threatening complications that often occur after therapy, such as severe infection and acute graft-versus-host disease (GVHD) (Horowitz et al, 1990; Gratwohl et al, 2002)
Summary
Successful HSCT or bone marrow transplantation involves the transplantation of new, functional immune systems after chemotherapy and radiotherapy. Allo-HSCT or bone marrow transplantation has been used successfully to treat hematopoietic malignancies, hematopoietic failure, autoimmune diseases, and genetic disorders (Copelan, 2006). The profiles of several serum proteins and peptides are altered during the processes of conditioning, stem cell infusion, and engraftment. Alterations in the serum proteome can reveal surrogate biomarkers, which can be assayed with relative ease to predict the outcomes and complications of allo-HSCT.
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