Serum erythropoietin in chronic lymphocytic leukaemia

Abstract

Anaemia is a frequent complication of advanced chronic lymphocytic leukaemia (CLL) and several cytokines known to inhibit erythropoietin (Epo) formation are produced by CLL B cells. Therefore we measured serum Epo levels in 47 CLL patients to determine whether Epo was a significant factor in the development of their anaemia. Epo levels were increased compared to normal individuals and this elevation appeared adequate for the degree of anaemia. The slope of the regression of Epo versus haemoglobin (Hb) was similar to that of a reference group. Serum transferrin receptor (sTfR) levels were also appropriately elevated for the degree of anaemia and correlated with serum Epo. Advanced stage was not associated with reduction of Epo production but diminished erythropoietic activity was observed in several patients. The results indicate that anaemia in CLL is not characterized by inadequate Epo production.

An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells

“…In the U.S., more than 100,000 new cases of blood-related cancers are diagnosed every year (see The Leukemia and Lymphoma Society's web page, www.leukemia.org). Leukemia and lymphoma cells, which are of hematopoietic origin, overexpress the TfR compared with normal tissues (6,9,14,15) and may be especially sensitive to the cytotoxic effect of anti-TfR. Furthermore, it is possible that tumor-specific cytotoxicity can be enhanced by using anti-human TfR IgG3-Av to deliver biotinylated cytotoxic molecules.…”

“…In normal tissues, constitutive expression of the TfR is limited to the liver, epidermis, intestinal epithelium, vascular endothelium of brain capillary, and certain populations of blood cells in the bone marrow (5)(6)(7)(8)(9). In contrast, high levels of TfR expression have been identified on many tumors (5,(10)(11)(12)(13)(14)(15). In fact, studies have shown that the TfR is expressed more abundantly in malignant tissues than their normal counterparts (5,13,16,17).…”

Soluble transferrin receptor for the evaluation of erythropoiesis and iron status

“…The significance of this is unclear. On the one hand, sTfR levels are not increased beyond what is expected if the bone marrow is capable of responding adequately to an appropriate Epo stimulation for the degree of anemia [17]. This would indicate that the pathogenesis of anemia in CLL is in large part related to hemolysis and/or hypersplenism.…”

“…Children with acute leukemia or solid tumors have adequate Epo production but profoundly suppressed erythropoiesis [16]. Patients with chronic lymphocytic leukemia (CLL) appear to have appropriate Epo production and erythroid marrow response for the degree of anemia, although erythropoiesis may become impaired in advanced stages [17]. A significant proportion of multiple myeloma patients has relative marrow failure in large part due to inadequate Epo production [18].…”

“…Patients with many lymphoid malignancies, including hairy cell leukemia and multiple myeloma, have been found to have normal sTfR values, but this represents relative marrow failure for the degree of anemia [12,18,130,135]. However, levels may be considerably elevated in chronic lymphocytic leukemia [17,130]. The significance of this is unclear.…”