Study Of Cytokine Expression Profile And Interleukin-3Receptor Isoforms Expression In Acute Leukemia

The growth, proliferation, differentiation and apoptosis of hematopoietic cells wereregulated by the regulatory networks which consists of positive or negative regulatoryfactors. Positive regulatory factors including IL-1, IL-3, IL-6, GM-CSF and G-CSF,etc while negative regulatory factors including TGF-β, TNF-α and IFN-γ, etc. Thepositive regulatory factors can promote hematopoietic cells proliferation anddifferentiation, and the negative regulators can inhibit hematopoietic cell proliferationand induce apoptosis. Leukemia is the hematopoietic system malignancies whichwere characterized by hampered cell differentiation and excessive proliferation.Therefore, hematopoietic regulatory factors plays an important role in leukemogenesis.We have found that the leukemia cell lines expressing a variety of positive cytokinesand its receptors. These cytokines were produced by autocrine or paracrine. There canstimulate theproliferation and inhibite the apoptosis of leukemic cells. There weresporadic reports of cytokine expressions and its significance in acute leukemia, buthave not systematic studies of these cytokines.In order to study the expression levelsof hematopoieticregulatory factors systematically in patients with acute leukemia,cytokinesincludingIL-1β,Il-2,IL-4,IL-5,IL-6,IL-7,IL-8,IL-10,IL-12,IL-13,IL-17,G-CSF,GM-CSF,INF-γ,MCP-1,MIP-1β,TNF-α,IL-3in serum from fifty-seven acute leukemia patientsweremeasured by protein chip technology andElisa.Serum from thirteen health personwere used as normal controls,comparing the expression differences of these factorsbetween acute leukemia and normal people.IL-3was a multi-colony stimulating factor which can promoting hematopoieticstem cell proliferation and differentiating to the myeloid stem cells and the precursorsof myeloid progenitor cells.IL-3play its biological functions by combining to the cellsurface receptor(IL-3R). The IL-3R were composed of αand β subunits. There were reports of acute leukemia patients highly expression IL-3than normal people.Both ourstudies and foreign researches have foundthat the acute myeloidleukemiaandacutelymphocytic leukemiaBhighexpressed IL-3R; acute myeloid leukemia patientswith high expression of IL-3Rα showed high white blood cell and high blast cell.These patients have low remission and high relapse rates, short disease-free survivaland poor prognosis.Recently, Our international partners found that both human and murine IL-3Rα hastwo different isomers: the traditional IL-3R, called SP1and the newly discoveredIL-3Rα which missing the N-terminal Ig-like domain, called SP2. In vitroexperiments found that murine FDCP-mix cells expressed human IL-3RαSP1showdself-renewal and proliferative capacites, while the same cells expressed humanIL-3RαSP2showed differentiate capacities. These results demonstrated that SP1andSP2were mediating different cellular signal transduction effects.The SP1has been reported highly expressd in acute leukemia,however,there is norelevant reports of the SP2. In this study, absolute quantitative RT-PCR was used tomeasure the expression of two isomers in acute leukemia cells.Results:1. The serum levels of IL-4、IL-5、IL-7、IL-12、GM-CSF、 IFN-γ、IL-13weredecreased in acute myeloid leukemia patients compared with healthy controls; thelevels of IL-10、MIP-1βand TNF-αwere increased; the levels of expression of IL-1β,IL-6,IL-8,IL-13,IL-17,G-CSF,MCP-1all shows no significant differencescompared with normal controls(P>0.05).2. The serum levels of IL-7、IFN-γ、IL-12、IL-3were lower compared withhealthy control in patients with acute lymphoblastic leukemia;the serum levels ofIL-10、MCP-1were higher compared with healthy controls in patients with acutelymphoblastic leukemia;the levels of expression of IL-1b，IL-4，IL-5，IL-6，IL-8，IL-13，IL-17，G-CSF, GM-CSF,IL-3all shows no significant differences comparedwith normal controls(P>0.05).3. The levels of IL-1β in AML patients were positively associated with blast cellproportion; the levels of IL-6in AML patients were positively associated with leukocyte count;the levels of IL-12and IFN‐γ in ALL patients were negativelyassociated with leukocyte count and negatively associated with blast cell proportion;the levels of IL-4and IL-7were positively associated with platelet count in ALpatients; the levels of MIP-1β were positively associated with leukocyte count in ALpatients.4. Expression levels of hIL-3RαSP1and hIL-3RαSP2were increased in ALpatients; expression levels of hIL-3RαSP1were higher than the expression levels ofhIL-3RαSP2in acute leukemia.Conclusion:1.Acute leukemia were associated with cytokine expressionprofilingdifferences,the levels of specific cytokines were closely related to leukocytecount, blast cell proportion and platelet count.2.Expression levels of hIL-3RαSP1and hIL-3RαSP2were increased in ALpatients;expression levels of hIL-3RαSP1were higher than the expression levels ofhIL-3RαSP2in acute leukemia.