Variation Of Expression Level And Activity Of Coagulation Factor X? Among Acute Leukemic Patients

BACKGROUND AND PURPOSECoagulation factor ??(F??),which can catalyze the cross-linking of fibrin to stabilize the clot,plays an important role in coagulation cascade.F?? is a transglutaminase(TG)that circulates in tetramericform(F??-A2B2),consisting of two A subunits(F???A2)and two B subunits(F??-B2)and can catalyze more than 140 substrates.It was found that F??-A2 expressionlevel of tumor cells was significantly elevated in patientswith acute myelomonocytic leukemia(AML-M4)and acutemonocytic leukemia(AML-M5).The author suggested thatF?? level could be used to differentiate myeloblast andmonoblast.Research on acute promyelocytic leukemia reported similar results.Elevated F??-A2 expression isalso found in neoplastic cells of ALL patients,even normal lymphocytes contained no F??-A2.Besides,as there is no standard way of measuring F?? activity,we hope to establish a method suitable for our department to help the diagnosis of F??-related disease in the future.We want to explore the role F?? played in those acute leukemic patients who were presented with bleeding symptoms.We also try to measure and analyze the concentration and activity of F?? in hemophilic patients,a typical disease with bleeding symptoms.METHODSThis study includes previously untreated acute leukemic patients at Peking Union Medical Hospital from November 2016 to May 2017.Both peripheral blood and bone marrow samples were collected.The method of enzyme-linked immunosorbent assay(ELISA)was adopted to measure F?? concentration in peripheral blood.The activity of F?? was measured by a kit and a coagulation analyzer.The RNA of mononuclear cells in both peripheral blood and bone marrow was extracted and used for quantitive real-time PCR(qRT-PCR)to determine the expression level of F?? messenger RNA(mRNA).F?? activity was analyzed in combination with the bleeding symptoms of patients.Both the concentration and activity of F?? were analyzed in hemophilic patients.RESULTSOur study included 31 previously untreated acute leukemic patients,among which 24 are acute myeloid leukemic(AML)patients and 7 are acute lymphoblastic leukemic(ALL)patients.F?? concentration of AML and ALL patients are 24.09(20.91)?g/mLand32.08±10.60?g/mL before treatment respectively,and decreased to 18.43±4.74?g/mLand19.21±8.69?g/mL after treatment respectively.F?? activity of AML patients is 72.75±28.98%before treatment and increased to 94.74±617.72%.F??activity of ALL patients also have a trend of increasing after treatment.For AML patients,the ? Ctof exon 3(? Ct exon3)and exon 14-15(? Ct exon14-15)of F?? A subunit(F??-A)gene of both peripheral blood and bone marrow mononuclear cells before treatment are similar to that of the control.For AML patients,? Ct exon3 and ? Ct exon14-15 of mononuclear cells from peripheral blood before treatment are 0.93±2.36 and 1.53±2.21 respectively and the corresponding value of bone marrow before treatment are 2.21±2.45and1.70±2.40 respectively.All of them has no significant difference from the control group.For ALL patients,? Ct exon3 and ? Ct exon 14-15 of mononuclear cells from peripheral blood before treatment are 1.49±1.43 and1.66±1.48 respectively and the corresponding value of bone marrow before treatment are 1.30± 1.58and1.85±2.94 respectively.All of them has no significant difference from the control group.The analysis of F?? activity and bleeding symptoms show no relation between F??activity and bleeding in acute leukemic patients.The concentration of F?? in hemophilic patients is 10.80±3.17?g/mL and 9.82±2.55?g/mL before and after treatment respectively.And the activity of F?? in hemophia A patients who presented with joint bleeding is 80.63±20.52%and80.87± 20.88%before and after treatment respectively,all of which are lower than normal(103.49±3.06%).CONCLUSIONSIt turns out that both AML and ALL patients have a reversed change of F??concentration and activity after treatment.F?? concentration decreased after treatment,while F?? activity increased.The F?? mRNA level of mononuclear cells from both peripheral blood and bone marrow before treatment is similar to that of the control group,suggesting that the tumor cells in peripheral blood and bone marrow is not related to the increased F?? level in peripheral blood.The bleeding symptom of acute leukemic patients is not related to decreased F?? activity.Patients of hemophilia A who presented with joint bleeding may also have F?? lower than normal.