TfR2 MRNA Expression In Bone Marrow Mononuclear Cells From Children With Hyperplastic Anemia:possible Implications

Objectives: The aim of this research is to study the expression of TfR2 mRNA in bone marrow mononuclear cells from children with hyperplastic anemia and control children, exploring the correlation between TfR2 mRNA expression to Hb conconcentration, bone marrow erythroid hyperplasia, body iron status and underlying diseases of hyperplastic anemia.Methods: Bone marrow mononuclear cells from 40 children with hyperplatic anemia and 10 control children without erythroid disorders and hematological maligancy were isolated using density gradient centrifugation. Expressions of TfR2 mRNA and house-keeping gene GAPDH mRNA were assayed by fluorescence quantitative PCR. In order to scale off initial RNA difference,TfR2 mRNA expression was represented by relative level, which is defined as the ratio of TfR2 copy numbers to GAPHD copy numbers.Results:1. The relative level of TfR2 mRNA expression in children with hyperplastic anemia was significantly higher than that in control children(p<0.001), with medians of relative expression levels of 5.58 in hyperplastic group and 0.0518 in control group respectively.2. TfR2 mRNA expression was negatively correlated to Hb concentration in peripheral blood (ranked correlation coefficient of-0.715, p<0.001). Althoug relative TfR2 mRNA expression from mild hyperplastic anemia group (median of 0.1971) was somewhat higher than that of control, it did not reach statistical significance. While the relative TfR2 expressions in moderate (median of 3.83) and severe hyperplastic anemia groups (median of 6.79) were statistically higher than that In control and mild hyperplastic groups, indicating that TfR2 mRNA expression was remarkably upregulated with deceasing Hb concentrations.3. There existed a positive correlation between relative TfR2 mRNA expression level and percentage of bone marrow erythroblasts (ranked correlation coefficient of 0.533, p<0.001). This was compatible to the finding that percentage of bone marrow erythroblasts was negatively correlated to Hb concentration in peripheral blood(ranked correlation coefficient of-0.488, p=0.001)4. The medians of relative TfR2 mRNA expression were 4.13 in IDA group, 7.63 in thalassemia group, and 2.34 in other hyperplastic anemia, respectively. Althoug significantly higher than that in contol group, there were no statistical differences among hyperplastic anemia groups with different underlying diseases.5. TfR2 mRNA expression was not correlated to body iron status, as judged by such parameters as SI, TIBC, serum ferrtin and TS.Conclusions:1. Marked up regulation of TfR2 mRNA expression in children with hyperplastic anemia strongly indicates that TfR2 might be closely involved in erythropoiesis, possibly serving as a iron regulator, or even as an erythroblast-specific iron transporter, given the fact that it is highly expressed in fetal hepatocytes and erythroblast.2. Our findings that TfR2 mRNA expression increases with decreasing Hb concentrations irrespective of the underlying diseases of hyperplastic anemia, and that TfR2 mRNA expression negatively correlated to Hb concentration but positively correlated to percentage of bone marrow erythroblast, strongly suggest that anemia itself is a powerful stimulator of TfR2 expression, and that TfR2 itself is a good indicator of erythroid hyperplasia, which might turn out to be useful in clinical practice in the differentiation of hyperplastic and hypoplastic anemias.