Promotion of the self-renewal capacity of human acute leukemia cells by Wnt3A.
BACKGROUND
Wnt/beta-catenin signaling is involved in the growth of various types of cancer cells. Wnt3A has been reported to promote the self-renewal of hematopoietic stem cells.


METHODS
The effects of recombinant Wnt3A protein on the in vitro growth of four acute myeloid leukemia (AML) and four acute T-lymphoblastic leukemia (T-ALL) cell lines was examined.


RESULTS
Wnt3A stimulation either had no effect on, or slightly suppressed, the short-term growth of these cell lines. In three cell lines, Wnt3A promoted clonogenic cell recovery after suspension culture, suggesting the promotion of the self-renewal capacity of leukemic stem or progenitor cells. Immunoblot analysis showed that Wnt3A stimulation reduced phosphorylated beta-catenin and increased beta-catenin in these cells, indicating that Wnt3A stimulation activated Wnt/beta-catenin signaling.


CONCLUSIONS
Wnt3A stimulation did not promote the growth of whole cell populations, but did promote the self-renewal of leukemic stem/progenitor cells in some AML and T-ALL cell lines.
Kawaguchi-Ihara
Noriko
N
Department of Laboratory Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
Murohashi
Ikuo
I
Nara
Nobuo
N
Tohda
Shuji
S
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000208:Acute Disease; D018952:Antigens, CD34 / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D000072099:Serrate-Jagged Proteins; D051153:Wnt Proteins / Q000494:pharmacology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011994:Recombinant Proteins; D000072099:Serrate-Jagged Proteins; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051997:ADP-ribosyl Cyclase 1