Clinical Study Of Leptin In Hematopoietic Tissue Of Aplastic Anemia

Backgroud and objective: Aplastic anemia (AA) is a common hematologic disease, which is characterized as hematopoietic stem cell and (or) hematopoietic microenvironment injuring and bone marrow pimelosis, so as to peripheral whole blood cells reducing. Leptin is one kind of protein, coded by obese gene (ob) of fat cells, which is composed of 167amino acid. In 1994, ob was first separated from fat cells of human and mouse. In 1995, the obese gene receptor (ob-R) was coded successfully. Ob-R belongs to type I cytokine receptors and is composed of 894 amino acid. It has uniquely primary structure and its secondary structure is similar to cytokine. Combining with its receptor, leptin can accommodate lipometabolism and has other more physiological functions. Recently studies display that it is important to accommodate the blood cells' proliferation and differentiation. We investigated leptin level of bone marrow and peripheral blood in patients with AA to find out the relationship betweenleptin and hematopoietic microenvironment abnormality under AA state.Methods: We divided subjects into four groups on the basis of normal persons, AA, acute leukemia (AL) and nutritional anemia. Each subject was collected bone marrow fluid and peripheral blood respectively and radioimmunoassay (RIA) was used to measure leptin level of them. Moreover, the patients of AA and AL were added to carry bone marrow biopsies, and their pathological sections was done to analyze area ratio of hematopoietic tissue, adipose tissue and bone trabecula.Results: The leptin level of bone marrow fluid and peripheral blood has high significant difference between the groups of normal persons, AA, AL and nutritional anemia (bone marrow fluid: F=10.98, PO.01; peripheral blood: F=11.35, P<0.01). And the level of AA group is significantly from the other groups (P<0.01), while the multiple comparison of the other three groups has no significant difference (P>0.05). The ratio of BM/PB between the four groups has high significant difference (F=6.45, PO.01). The ratio of AA group is higher than the other groups, while the multiple comparison of the other three groups has no significant difference (P>0.05). Thedegree of anemia has no correlation with leptin level (P>0.05), but the relationship of leptin level of bone marrow fluid and peripheral blood is positive correlation, and their coefficient of correlation is highly significant different (P<0.01). The bone marrow pathological sections display that: myloproliferative degree of AA is reducible or reducible extremely, hematopoietic cells decrease obviously and adipose cells increase obviously, bone trabecula decrease seriously or disappear. While myloproliferative degree of AL is active or active extremely, the marrow is filled with rich metamyelocytes and adipose cells decrease obviously or disappear, but bone trabecula can be seen. High significant difference exists between AA and AL of the areas of their hematopoietic tissue, adipose tissue and bone trabecula.Conclusions: Fat cells in bone marrow can produce leptin. The leptin content in blood circulation probably comes from the secretion of peripheral and bone marrow fat cells. The leptin level of bone marrow and peripheral blood from patients with AA is significantly higher than those of normal persons, AL or patients with nutritional anemia, probably be related to the remarkable increase of fat cells in bone marrow of AA. Incomplete leptin receptors and low responsiveness ofhematopoietic stem/progenitor cells to stem cell factors may destroy the synergic stimulation effects of leptin and stem cell factors on proliferation of primitive hematopoietic progenitors. At the same time, the level of tumor necrosis factor a (TNF a ) is much more higher, which makes mass CD34+ cells apoptosis. And TNF a activates ob gene expression by inducing cells signal transduction to increase the leptin level. Summing up the above three causes may be the reason of why AA patients have high leptin level but low hematopoietic stem/progenitor cell number and peripheral whole blood cells reducing.