Effect of thrombopoietin on acute myelogenous leukemia blasts

It has been shown that the expression of c-mpl, which is a Specific recepto r for thrombopoietin (TPO), is restricted to the surface of megakaryocytes, platelets, human CD34(+) progenitor cells and human erythroid/megakaryocyt ic leukemic cell lines. Recently, however, it has been reported that some a cute myelogenous leukemia (AML) blasts expressed c-mpl on their cell surfac e 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 a nd 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 H-3-thymid ine incorporation, while synergistic stimulatory effects of TPO with stem c ell factor (SCF), interleukin-3 (IL-3), granulocyte colony-stimulating fact or, and granulocyte-macrophage colony-stimulating factor were observed in b oth groups. In a leukemic blast colony assay, significant growth response t o TPO was observed in 5/6 CD7(+) and 4/17 CD7(-) AML cases examined. Furthe rmore, 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(+) le ukemic blasts express functional TPO receptors and proliferate-in response to TPO. Thus CD7 expression on AML blasts may indicate the involvement of l eukemic 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.