Levels of p53 protein increase with maturation in human hematopoietic cells.
Transfection of the wild-type p53 gene into malignant cell lines usually results in an inhibition of proliferation. However, the physiological function of the endogenous p53 gene product has been difficult to ascertain. In order to examine whether p53 is involved in the regulation of proliferation and/or differentiation of hematopoietic tissue, we modified a recently developed flow cytometric assay to assess p53 protein expression in normal human hematopoietic cells, primary leukemias, and selected leukemia cell lines. In normal human bone marrow, p53 protein was not detected in the proliferative, progenitor cell populations identified by the cell surface antigens CD34 (progenitor cells of multiple lineages) or glycophorin (erythroid precursors). In contrast, low but detectable levels of p53 protein were observed in the nonproliferative, mature lymphoid, granulocytic, and monocytic cell populations. Similarly, p53 levels increased and DNA synthesis decreased during 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of ML-1 myeloblastic leukemia cells. Both of these results suggest that endogenous, wild-type p53 protein may play a role in hematopoietic cell maturation, possibly by contributing to the inhibition of proliferation that occurs during terminal differentiation. Leukemia cells deviated from this pattern of expression: (a) in contrast to the normal, proliferative bone marrow progenitor cells, a significant percentage of patient leukemia samples expressed detectable levels of p53 protein; and (b) leukemia cell lines exhibited lineage-specific abnormalities in p53 expression, with overexpression in lymphoid cell lines and lack of expression in myeloid cell lines.
Kastan
M B
MB
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Radin
A I
AI
Kuerbitz
S J
SJ
Onyekwere
O
O
Wolkow
C A
CA
Civin
C I
CI
Stone
K D
KD
Woo
T
T
Ravindranath
Y
Y
Craig
R W
RW
D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D009842:Oligopeptides; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D013755:Tetradecanoylphorbol Acetate