Effects of thrombopoietin (c‐mpl ligand) on growth of blast cells from patients with transient abnormal myelopoiesis and acute myeloblastic leukemia

Abstract

Thrombopoietin (TPO) is a ligand for c‐mpl that promotes both proliferation and differentiation of megakaryocytes in vivo and in vitro. We investigated the expression of c‐mpl transcripts and the effects of recombinant human TPO (rhTPO) on the proliferation and differentiation of human leukemic cell lines or fresh samples obtained from 32 patients with transient abnormal myelopoiesis (TAM) or acute myeloblastic leukemia (AML). Cells were cultured with TPO alone or combined with rh interleukin‐3 (IL‐3) or stem cell factor (SCF). Expression of c‐mpl was verified in 6 of 13 cases tested. All but one of the cases that showed c‐mpl expression responded to TPO. Blasts from all cases of TAM or French–American–British (FAB) subtype M7 showed growth responses to TPO with higher sensitivity than cells of other FAB subtypes and these responses were increased by addition of rhIL‐3 or rhSCF in some cases. Responses of cells of other FAB subtypes varied. In addition, increased expression of platelet‐specific surface antigens on MO7E cells after incubation with rhTPO was observed. These data suggest that TPO may be involved in the abnormal proliferation and differentiation of human leukemic cells, especially of M7 and TAM cells, considered to be of megakaryocytic lineage.

Hematopoietic stem cell differentiation affects expression and function of MRP4 (ABCC4), a transport protein for signaling molecules and drugs

“…When M‐07e cells are incubated with TPO, they undergo differentiation toward megakaryocytes 35. This is demonstrated in an experiment representative for at least 3 independent differentiation procedures by a shift in the geometrical mean of fluorescence intensity when cells were labeled for CD61 (glycoprotein IIIa) from 2.9 to 8.6 (negative control: 1.9; Fig.…”

“…These included the megakaryoblastic cell line M‐07e, the promyelocytic leukemia HL‐60 cells and the myelomonocytic cell line U937. These are pluripotent cells capable of undergoing differentiation along lineage specific pathways in response to a variety of agents 35–40. M‐07e cells were differentiated toward megakaryocytes with TPO, proven by CD61 expression and reduction of CD71.…”

“…M‐07e is a cytokine‐dependent subline of the myeloid leukemic cell line M‐07 derived from a patient with megakaryoblastic leukemia 33, 34. An increase of platelet‐specific antigens after incubation with TPO (c‐mpl ligand) has been described previously suggesting megakaryocytic differentiation 35. HL60 is a promyeloblastic leukemic cell line of a patient with acute promyeloblastic leukemia without translocation.…”

Sipa1 deficiency–induced bone marrow niche alterations lead to the initiation of myeloproliferative neoplasm

“…50,53 THPO-MPL signaling is critical for maintaining HSCs in adult BM 54 and is involved in the pathogenesis of MPN. 55,56 The upregulation of Thpo in the Sipa1 2/2 BM stromal cells may be associated with the enhanced granulopoiesis and the overproduction of MEPs and MK hyperplasia in the aged Sipa1 2/2 mice under steady state and after transplantation. The increased number of MKs in BM might in turn promote the progression of the MDS/MPN via platelet factor secretion, as described recently.…”

Protective effects on myelosuppression mice treated by three different classic chinese medicine formulae

“…Research data suggest that TPO may be involved in the abnormal proliferation and differentiation of human leukemic cells, especially of M7 and transient abnormal myelopoiesis (TAM) cells, considered to be of megakaryocytic lineage. [14]…”