Effect of thrombopoietin on proliferation of blasts from CD7-positive acute myelogenous leukaemia.
We investigated the effect of thrombopoietin (TPO) on the growth of leukaemic blasts from 30 acute myelogenous leukaemia (AML) patients according to the surface expression of CD7 and CD34: 10 patients were CD7 positive (CD7+), nine were CD7 negative/CD34+ (CD7-/CD34+) and the remaining 11 were CD7-/CD34-. Significant growth response of leukaemic blasts to TPO was observed in 10/10 CD7+, 5/9 CD7-/CD34+ and 2/11 CD7-/CD34- AML cases using 3H-thymidine incorporation. 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 TPO-responding cases (9/17) and TPO-non-responding cases (8/13). In a leukaemic blast colony assay. significant growth response to TPO was observed in 5/6 CD7+ and 4/17 CD7-AML cases examined. However, the effect of TPO on the growth of CD7+ leukaemic blasts was not so potent as that of IL-3 and SCF, both of which support the proliferation of primitive haemopoietic progenitors. Expression of c-mpl (TPO receptor) was significantly higher in CD7+ AML cases than in CD7- cases, suggesting a relationship between expression of c-mpl and proliferative response to TPO. These data indicate that CD7+ leukaemic blasts express functional TPO receptors and proliferate in response to TPO. These observations also imply that CD7 expression on AML blasts may indicate involvement of leukaemic progenitors at an early stage of multipotent haemopoietic stem cells.
Tokunaga
Y
Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Miyamoto
T
T
Okamura
T
T
Eto
T
T
Gondo
H
H
Kamimura
T
T
Okamura
S
S
Niho
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D019011:Antigens, CD7 / Q000378:metabolism*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D018952:Antigens, CD34; D019011:Antigens, CD7; D004273:DNA, Neoplasm; D007377:Interleukin-3; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; C082218:MPL protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin