Mast cell growth factor, a ligand for the receptor encoded by c-kit, affects the growth in culture of the blast cells of acute myeloblastic leukemia.
The c-kit proto-oncogene encodes a transmembrane receptor with a tyrosine kinase internal domain. C-kit has been mapped to the W locus in the mouse, and the gene encoding the ligand has been shown to be the product of the murine SI locus. Previous genetic studies have shown that the murine W and SI loci play important roles in the normal function of hemopoietic stem cells. As these stem cells have been identified as the origins of abnormal clones in acute myeloblastic leukemia (AML), a study was begun of c-kit in AML. By Northern blot analysis, it was shown that all of 21 blast populations from AML patients were kit expression positive, but some AML cell lines did not transcribe detectable c-kit mRNA. This study is now extended to the responses of freshly obtained AML cells and cell lines to the ligand, mast-cell growth factor (MGF). In culture, fresh cells usually responded to added ligand with increases in both self-renewal and terminal divisions. The most obvious effects were seen when MGF was combined with either IL-3 or G-CSF. The response of cell lines to MGF mirrored their expression of c-kit; expression positive lines responded in culture with patterns similar to those seen for fresh cells. C-kit expression negative cells did not respond to MGF. RNA prepared from the cells giving rise to one such line, OCI/AML-5, was available for study. mRNA for c-kit could not be detected in this RNA sample by Northern blot analysis or the polymerase chain reaction. Thus the heterogeneity found in AML blast populations extends to the involvement of c-kit and its ligand in growth regulation, although blast populations without this regulatory apparatus appear to be rare.
Wang
C
C
Ontario Cancer Institute, Toronto, Canada.
Koistinen
P
P
Yang
G S
GS
Williams
D E
DE
Lyman
S D
SD
Minden
M D
MD
McCulloch
E A
EA
D002455:Cell Division; D004357:Drug Synergism; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor