A Study By Platelet Proteomics Technology In Childhood Acute Lymphocytic Leukemia

Objective Acute lymphocytic leukemia(ALL) is one of the mostcommon hematological malignancies in children, the bleeding complicationsare very common in acute leukemia and often lead to death. The mechanism ofbleeding is complex, one major reason for the high risk of hemorrhage isthrombocytopenia. Besides the decline in platelet counts, there may be plateletfunction defects. It is still not fully understanding the pathological mechanismof platelet dysfunction in ALL with little study right now. The study aims toanalyze the differently expressed platelet proteins of the state of children acutelymphocytic leukemia (ALL) by platelet proteomics technology, andinvestigate the molecular mechanism of abnormal platelet function caused byALL, so as to provide positive intervening measures at early stage forhemorrhage in order to improving prognosis of the disease. Method Thecomplete set of platelet proteins spectrum were obtained by using CM10protein chip and the surface enhanced laser desorption/ionization time-of-flightmass spectrometry (SELDI-TOF-MS),27cases were of the new diagnosis ofacute lymphocytic leukemia(ALL),25cases of ALL in first complete remission(ALL-CR1) and27cases of healthy children as a contrast group. TheBiomarker Wizard and Biomarker Pattern System5.0were used to analyzingthe different proteins and screened the proteins related platelet function with significant difference. Results (1) In the range of mass-to-charge ratio2000～20000,176protein mass peaks were found differences in expressingbetween the ALL and the control group（p<0.05）,25peaks of which were ofhigh expression and151with low expression. The protein peaks with stableexpression and low coefficient of variation were9,2peaks were highexpression with mass-to-charge ratio(M/Z) of2496.87and4287.92;7peakswere low expression with mass-to-charge ratio(M/Z) of7881.2、4091.3、3149.9、2365.1、9414.1、5252.3、2280.7.(2)112protein mass peaks were founddifferences in expressing between the ALL and the ALL-CR1（p<0.05）,15peaks of which were of high expression and97with low expression. Theprotein peaks with stable expression and low coefficient of variation were6,2peaks were high expression with mass-to-charge ratio(M/Z) of2496.87and4287.92;4peaks were low expression with mass-to-charge ratio(M/Z) of9414.1、7881.2、3149.9、2280.7.(3)There is no high expressed protein peakwith significant difference between the ALL-CR1and the control, but still were69peaks down-expressed.(4)The nine proteins with statistically significantwere obtained from protein database between ALL and the control group, thetwo up-expressed proteins were Endothelin-1and Big Endothelin-1,thedown-expressed proteins are Platelet factor4, Thrombin light chain, Pituitaryadenylate cyclase-activating polypeptide27, Fibrinogen bata chain and threeunknown proteins. These may be associated with the platelet signaltransduction, adhesion, aggregation and activation, etc. Conclusion (1)There is significant difference between the platelet proteomics of ALL and childhoodhealthy;(2)There is also significant difference between the platelet proteomicsof ALL and ALL-CR1, while during complete remission after induction therapythe number of abnormal expressed proteins were decreased, but some of themstill with low expression;(3) There may be functional platelet defects in ALL,mainly in the dysfunction of cell signaling transmission, the decrease ofaggregation and activation and the abnormal of coagulation;(4) The study willprovide a new way for monitoring the function of platelet of ALL.