| IntroductionRecent studies indicated that TfR2, the newly identified TfR1 homologue, could bind to TfR1 and possibly inhibite TfR1-mediated cellular iron uptake. In addition, TfR2 mRNA was expressed in all FAB types of acute myeloid leukemia, and elevated TfR2 expression was even found to be a favorable prognostic factor for AML patients. However, little is known about the expression of TfR2 in childhood acute leukemia and possible clinical correlations.ObjectiveThe aim of this research is to study the expression of TfR2 mRNA in bone marrow or peripheral blood mononuclear cells from children with acute leukemia. In addition, it also sets out to explore possible correlations between TfR2 expression and a panel of prognostic/risk factors.MethodsTotal cellular RNA was isolated from bone marrow or peripheral blood mononuclear cells from 82 cases of childhood acute leukemia(including 56 ALL and 26 AML) and was retrotransrcibed to cDNA with ReverTraAce retrotranscription kit. Expressions of TfR2 mRNA and house-keeping gene GAPDH mRNA were assayed by fluorescence quantitative PCR. In order to normalize initial RNA sampling and loading differences, TfR2 mRNA expressionwas represented by relative level, which was defined as the ratio of TfR2 copy numbers to GAPHD copy numbers.Results1. There were no significant differences between relative expression levels of TfR2 in mononuclear cells from children with acute leukemia and control children(P=0.588), with medians of 0.0360 and 0.0693 in AL group and control group respectively.2. TfR2 was expressed in all AML patients and all except one ease of ALL. The expression level of TfR2 in ALL group was compatible to that in AML group, though tended to be lower in AML(median of 0.0172) than that in ALL(median of 0.0474).3. The relative expression level of TfR2 was well correlated to prednisone responsiveness, clinical risk and initial WBC counts. The medians of TfR2 expression levels were 0.0848 and 0.0126 in prednisone good responders and prednisone non-responders respectively(P=0.038), 0.1677, 0.0728 and 0.0125 in LR, MR and HR ALL groups respectively(P=0.003). In addition, ALL patients with higher intitial WBC count over 100×10~9/L had significantly lower TfR2 expression (median of 0.0078) than those with intiatial WBC count less than 50×10~9/L (median of 0.0974).4. TfR2 expression levels were found to be negatively correlated to initial WBC count, percentage and absolute number of blast cells in peripheral blood, with ranked correlation coefficients in each case of -0.398, -0.307 and -0.421 respectively.5. Although TfR2 was expressed in all AML cases, the present study did not reveal correlation of TfR2 expression to any prognostic/risk factors. Conclusions1. Although no significant difference of TfR2 expression levels exists between AL group and control children, lower TfR2 expression in AL patients might impose leukemic cells with greater iron uptake capacity and thus greater proliferation potential, given the fact that TfR2 can bind to TfR1, and therefore reduce TfR1-mediated cell iron uptake via endocytosis.2. Our research findings that TfR2 expression was positively correlated to prednisone responsiveness, negatively correlated to clinical risk stratefication, initial WBC count and blast cell percentage/absolute numbers in peripherial blood, suggest that TfR2 might be an novel and important prognostic factor for ALL prognistification.3. The findings that there were elevated TfR2 mRNA expressions in prednisone-responsive ALL, in ALL with lower initial WBC count and in low-risk ALL are consistent, and lead us to the speculation that elevated TfR2 expression might inhibit TfR1-mediate iron uptake by leukemic cells, resulting in reduced proliferation potential and better clinical prognosis.4. TfR2 expression tends to be lower in AML than that in ALL, though without significant difference. It remains to be clarified whether it is related to poor therapeutic response and clinical prognosis of AML as compared to ALL.
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