Effects of flt3 ligand on acute myeloid and lymphocytic leukemic blast cells from children.
A ligand for the flt3 tyrosine kinase receptor (flt3R) has recently been cloned. Forty-three cases of childhood acute myeloid leukemia (AML) and 27 cases of childhood acute lymphocytic leukemia (ALL) were examined by flow cytometric analysis for cell-surface flt3R and proliferative response in vitro to flt3 ligand (flt3L). Flt3R was commonly expressed on the cell surface of leukemic cells from all AML subclasses and B-ALL, but we did not detect cell-surface flt3R on T-ALL. Flt3L alone induced the proliferation of the monocytic AML-M5 cells and some erythroleukemic AML-M6 cells. Some isolated instances of weak proliferative responses were also noted in other AML subclasses. Interleukin-4 (IL-4) alone inhibited the proliferation of a group of AML-M5 cells and, when combined with flt3L, suppressed the proliferative effect of flt3L. In general, B-ALL and T-ALL cells failed to respond to flt3L alone or in the presence of combinations of IL-2, IL-3, or IL-7.
McKenna
H J
HJ
Immunex Research and Development Corp., Seattle, WA 98101, USA.
Smith
F O
FO
Brasel
K
K
Hirschstein
D
D
Bernstein
I D
ID
Williams
D E
DE
Lyman
S D
SD
D000208:Acute Disease; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002648:Child; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000473:pathology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008565:Membrane Proteins / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051941:fms-Like Tyrosine Kinase 3
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3