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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4167-4178
Expression of p21Cip1/Waf1/Sdi1 and p27Kip1
Cyclin-Dependent Kinase Inhibitors During Human Hematopoiesis
Toshiyasu Taniguchi,
Hisako Endo,
Norio Chikatsu,
Kaoru Uchimaru,
Shigetaka Asano,
Toshiro Fujita,
Tatsutoshi Nakahata, and
Toru Motokura
From the Fourth Department of Internal Medicine, the Department of
Pathology, the Branch Hospital, School of Medicine, and the Departments
of Hematology/Oncology and Clinical Oncology, Institute of Medical
Science, University of Tokyo, Tokyo, Japan.
Expression of p21 and p27 cyclin-dependent kinase inhibitors is
associated with induced differentiation and cell-cycle arrest in some
hematopoietic cell lines. However, it is not clear how these inhibitors
are expressed during normal hematopoiesis. We examined various human
hematopoietic colonies derived from cord blood CD34+
cells, bone marrow, and peripheral blood cells using a quantitative reverse transcription-polymerase chain reaction assay, immunochemistry, and/or Western blot analysis. p21 mRNA was expressed increasingly over
time in all of the colonies examined (granulocytes, macrophages, megakaryocytes, and erythroblasts), whereas p27 mRNA levels remained low, except for erythroid bursts. Erythroid bursts expressed both p21
and p27 mRNAs with differentiation but expressed neither protein, whereas both proteins were expressed in megakaryocytes and peripheral blood monocytes. In bone marrow, p21 was immunostained almost exclusively in a subset of megakaryocytes and p27 protein was present
in megakaryocytes, plasma cells, and endothelial cells. In
megakaryocytes, reciprocal expression of p27 to Ki-67 was evident and
an inverse relationship between p21 and Ki-67 positivities was also
present, albeit less obvious. These observations suggest that a complex
lineage-specific regulation is involved in p21 and p27 expression and
that these inhibitors are involved in cell-cycle exit in megakaryocytes.

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