Abstract
Dysregulation of cytokines and growth factors is a general feature of tumor microenvironment, and unraveling the expression spectrum of cytokine and growth factor in niche is of utmost importance. Here, we evaluated cytokine profiling of bone marrow serum samples in AML patients and healthy controls. Protein expression profiling of serum from nine AML patients and five healthy controls was obtained using a biotinylated antibody chip. A total of 507 cytokines and growth factors were analyzed. Compared with healthy people, AML patients expressed 31 signature proteins, among which, 27 were significantly higher expressed and 4 proteins were lower. When patients were divided into favorable and poor prognosis, 12 signature proteins were significantly differentially expressed between these two groups. Furthermore, in order to identify the accuracy of cytokine expression profiles, we verified and analyzed the expression of THBS1 (Thrombospondin 1) in 116 patients and 9 healthy people. We found that THBS1 was lowly expressed in AML patients, which might be induced by promoter methylation, and patients with low THBS1 possessed shorter survivor time. Our data indicated that we successfully unveil differentially expressed proteins in AML patients using a biotinylated antibody chip; among them, THBS1 may be a potential therapeutic target for AML patients' treatment.
Highlights
Acute myeloid leukemia (AML) is a phenotypic and genetically heterogeneous hematological disease, curable in 30–50% of younger patients [1, 2]
We found that THBS1 was lowly expressed in AML patients, which might be induced by promoter methylation, and patients with low THBS1 expression possessed shorter survivor time; allogenic hematopoietic stem cell transplantation could conquer the bad effect mediated by THBS1 low expression
The interaction of leukemia cells and the surrounding microenvironment in the bone marrow is very important for leukemogenesis; a better understanding of the cytokine expression spectrum in the BM niche could contribute to prognosis improvement and potential target investigation
Summary
Acute myeloid leukemia (AML) is a phenotypic and genetically heterogeneous hematological disease, curable in 30–50% of younger patients [1, 2]. Cytogenetic and molecular genetic detection has become the main basis in the clinical risk classification of AML [3, 4]. It has been demonstrated that the extensive genetic abnormalities play an important role in the diagnosis, risk assessment, and determination of the prognosis of patients. According to the United States National Comprehensive Cancer Network (NCCN) guideline, the risk classification of AML can be divided into favorable, intermediate, and poor prognosis [5]. In real clinical practice, many patients with favorable prognosis showed low sensitivity or no response to standard treatment strategy. Further investigation of risk classification biomarker is needed
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