Effects of thrombopoietin (c-mpl ligand) on growth of blast cells from patients with transient abnormal myelopoiesis and acute myeloblastic leukemia.
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.
Hirai
H
H
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Shimazaki
C
C
Yamagata
N
N
Goto
H
H
Inaba
T
T
Kikuta
T
T
Sumikuma
T
T
Sudo
Y
Y
Ashihara
E
E
Fujita
N
N
Hibi
S
S
Imashuku
S
S
Ito
E
E
Nakagawa
M
M
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000473:pathology*; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D013926:Thrombopoietin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human; D013926:Thrombopoietin