Effect of Thrombopoietin on Acute Myelogenous Leukemia Blasts

Abstract

It has been shown that the expression of c-mpl, which is a specific receptor for thrombopoietin (TPO), is restricted to the surface of megakaryocytes, platelets, human CD34⁺ progenitor cells and human erythroid/megakaryocytic leukemic cell lines. Recently, however, it has been reported that some acute myelogenous leukemia (AML) blasts expressed c-mpl on their cell surface and proliferated in response to TPO. We therefore investigated the effect of thrombopoietin on the growth of leukemic blasts from patients with CD7-positive acute myelogenous leukemia (AML), which is a distinct biological and clinical subtype of AML. Significant growth responses of leukemic blasts to TPO were seen in 10/10 CD7⁺ and 7/20 CD7 AML cases using ³H-thymidine incorporation, while synergistic stimulatory effects of TPO with stem cell factor (SCF), interleukin-3 (IL-3), granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were observed in both groups. In a leukemic blast colony assay, significant growth response to TPO was observed in 5/6 CD7⁺ and 4/17 CD7⁻ AML cases examined. Furthermore, the expression of c-mpl seemed to be higher in CD7⁺ AML cases than in CD7⁻ cases, suggesting a relationship between the expression of c-mpl and the proliferative response to TPO. These findings imply that CD7⁺ leukemic blasts express functional TPO receptors and proliferate in response to TPO. Thus CD7 expression on AML blasts may indicate the involvement of leukemic progenitors at an early stage of multipotent hemopoietic stem cells. In this review, we discuss the effect of TPO on AML blasts, especially in CD7⁺ AML cases.

Key Words:

• acute myelogenous leukemia
• CD7
• thrombopoietin
• c-mpl