Primary acute myeloid leukemia cells negative for c-kit receptor protein expression do not proliferate in vitro in response to colony-stimulating factors.
This study examined the effects of recombinant human stem cell factor (SCF) alone or in combination with colony-stimulated factors (CSFs) on colony formation of leukemic progenitors obtained from 29 acute myeloid leukemia (AML) patients. C-kit receptor (c-kitR) protein expression was examined using an immunofluorescence method and was detected on more than 10% of leukemic cells in 20 of 29 cases (c-kitR+). SCF alone could stimulate formation of colonies in 14 of 20 c-kitR+ cases. Granulocyte(G)-CSF, granulocyte-macrophage (GM)-CSF, and interleukin (IL)-3 alone stimulated colony growth in 18, 17 and 16 of c-kitR+ cases, respectively. In contrast, colony and cluster formations from eight of nine c-kitR- cases was not stimulated at all by SCF alone nor SCF in combination with CSF nor with any CSF alone. However, the in vitro culture behavior of fluorescence-activated cell sorter-sorted c-kitR- cells from c-kitR+ cases did not significantly differ from c-kitR+ cells. These results suggest that responses of leukemic progenitors to CSFs were variable but may be predicted by their c-kitR expressions, and that c-kitR(-) cases may have a different disease entity from c-kitR(+) cases.
Hirakawa
K
K
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
Kimura
S
S
Chikayama
S
S
Misawa
S
S
Maekawa
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; 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; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit