Tyrosine phosphorylation of proteins in primary human myeloid leukemic cells stimulated by macrophage colony-stimulating factor: analysis by disease type and comparison with normal human hematopoietic cells.
We investigated tyrosine phosphorylation of proteins in primary human leukemic cells stimulated by macrophage colony-stimulating factor (M-CSF) in 60 patients with acute myeloid leukemia (AML) and 5 patients with chronic myelomonocytic leukemia and compared the findings for leukemic cells with those of normal human monocytes and bone marrow immature hematopoietic cells. M-CSF induced tyrosine phosphorylation of p140-200, p110, p60, p44, and p42 frequently, and that of p95 and p55 less frequently, in primary myeloid leukemic cells, whereas M-CSF-induced phosphorylation of proteins was not detected in the normal human hematopoietic cells tested. Of these phosphoproteins, p140-200 was phosphorylated in all patients who responded to M-CSF and was considered to be almost identical to Fms, a product of the c-fms proto-oncogene. M-CSF-induced tyrosine phosphorylation was observed frequently (89%) in AML of French-American-British class M4 and infrequently in all other subtypes of AML, including M5. In chronic myelomonocytic leukemia, M-CSF-induced protein phosphorylation was prominent in blast crisis but was not detected in the chronic phase. Both bone marrow immature cells and mature monocytes showed low responsiveness to M-CSF. These findings for responsiveness to M-CSF were correlated with the amount of Fms in each type of cell. We also identified tyrosine phosphorylation of Vav, Shc, and extracellular signal-regulated kinase by M-CSF in some cases. These findings clarified an M-CSF-specific pattern of protein tyrosine phosphorylation and the responsiveness to M-CSF of primary human myeloid cells. Particularly, enhanced phosphorylation responses to M-CSF and increased amounts of Fms protein were observed in restricted human hematopoietic cells with a premature myelomonocytic character.
Hagiwara
S
S
Department of Hematology, Research Institute and Hospital, International Medical Center of Japan, Tokyo.
Yagisawa
M
M
Saeki
K
K
Iki
S
S
Urabe
A
A
Mimura
T
T
Miwa
A
A
Togawa
A
A
Higashihara
M
M
Takaku
F
F
Yuo
A
A
D000208:Acute Disease; D000581:Amidohydrolases; D000626:Aminopeptidases / Q000378:metabolism; D018929:Cell Culture Techniques; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000473:pathology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D019089:Stem Cell Factor; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase