Expression Of Transferrin Receptors In Adult Patients With Acute Leukemia And Its Possible Clinical Implications

Background and aim:Our previous study on the proteomics of acute myeloblastic leukemia of M2-subtype (AML-M2) has found that the expression of transferrin receptor(TfR)were increased in both CD34+and CD34-cells from the patients with AML-M2. Except the function in iron metabolism, recent research suggested that TfR may invove in the tumorigenesis due to the abnormal expression in neoplasms. Several studies have reported high expression of TfR in leukemia, which means TfR may paly an important role in leukemic cell proliferation, but, all these works only focused on the transcription level of TfR, i.e, detecting TfR mRNA expression. Especially, it has presently no any reported about the study on TfR protein expression in adult acute leukemia (AL) Therefore, in this study, the expressions of the two-kind of TfR, i.e., TfR1and TfR2, were thoroughly analysed at the levels of both transcription and translation in the patients with AML and acute lymphoblastic leukemia (ALL) by revers transcription-polymerase chain reaction (RT-PCR), flow cytometry,(FCM) and Western blot (WB) technicals. Moreover, the possible clinical implication of TfR1and TfR2expressions in AL were analysed. We believe that this work might set a foundation for further study on the role of TfR in AL.Methods:Firstly, mononuclear cells were isolated from the newly diagnosed patients with AL and from peripheral blood lymphocytes of hematopoietic stem cell transplantation donors after mobilization, using lymphocyte separation solution. Secondly, TfRl and TfR2mRNA expressions in mononuclear cells of the AL patients were detected by RT-PCR method. Finally, the protein expressions of TfRl and TfR2in mononuclear cells of the AL patients were detected by flow cytometric or WB method, respectively. Based on these results, the possible clinical implications of TfR expression were analysed.Results:(1) The results of this study show, TfRl mRNA expression rate in the normal group, AML and ALL group were100%,55.2%and63.6%. Statistical analysis showed that these three groups of TfR1mRNA expression rate was no significant difference in the overall (P=0.063), the normal group and ALL group, ALL group and AML group patients, TfR1mRNA expression rate was not statistically different(P=0.10,P=0.730), but between the normal and the ALL group, TfR1mRNA expression rate had statistically significant difference(P=0.032).After electrophoresis, scanning, semi-quantitative PCR products of each gray value with internal reference gray value ratio, the results showed that the normal group, AML and ALL group TfRl mRNA expression levels were0.1912,0.2049and0.2027. Statistical analysis showed that every two groups of the three groups,TfRl mRNA relative expression had no significant difference (P>0.05). Meanwhile, the study founded that the normal group, AML and ALL groups, TfR2mRNA expression rates were12.5%,55.2%and9.0%, TfR2mRNA expression rate of three groups overall had significant statistical difference (P=0.008),there was no significant difference between the normal group and ALL group (P=0.811), but the normal group and the AML group, ALL and AML patients group had statistically difference (P=0.032, P=0.012).(2) Further analysis of TfR protein levels founded that the normal group did not express TfR1protein, and AML and ALL group expression rates were9.1%and17.2%. Statistical analysis showed that TfR2protein expression of three groups had no statistical difference overall (P=0.395), ALL and AML group had no significant difference (P=0.381, P=0.207), compared with normal group.ALL and AML group also statistically difference (P=0.519). Meanwhile, the normal group and the ALL group TfR2protein can not be detected, but the AML group TfR2protein expression was55.6%in AML group,which was statistically different from the overall expression (P=0.000),there was also statistical difference between normal AML group (P=0.001), ALL group and the AML group (P=0.005).(3) Clinical data analysis showed that both the mRNA or protein, TfRl and TfR2expression rate of AL patients in each group with age, sex, initial white blood cell count, the percentage of bone marrow blasts was no significant correlation (P>0.05); TfRl mRNA and protein expression were of no significant correlation (P=0.730, P=0.519) with classification of AML was, but TfR2mRNA and protein expression rate of AML highly correlated (P=0.012, P=0.001), acute myeloid leukemia expression significantly increased. Similarly, there was no correlation (P>0.05)between TfR1mRNA relative expression levels and the patient’s age, initial peripheral WBC count, Hb, LDH.TfR2(mRNA and protein) relative expression levels had no correlation with age initial peripheral WBC count, Hb, LDH(P>0.05). But TfR2(mRNA and protein) relative expression levels of LDH showed a significant negative correlation (r=-0.670, r=-0.760).Conclutions:The similar expression level of TfRl between AL patients and normal subjects may indicate no association of TfRl with AL. However, signifant increased expression of TfR2in AML patients than that of normal subjects and ALL patients suggests that TfR2may paly a role in the AML, and it may be able to use to diagnose AML and differentially diagnose AML with ALL. Furthermore, negative correlation of TfR2expression with AL burden may indicate the role of TfR2in prognostic valuation for AL.