EXPRESSION OF P15(INK4B) IN NORMAL HEMATOPOIESIS

The Cyclin-dependent kinase inhibitor (CDKI) p15(INK4B) (p15) induces cell cycle arrest in G0/G1 phase. Several studies report deletion or t ranscriptional loss of the p15 gene in myeloid and lymphoid hematologi cal malignancies, and a possible role as a tumor suppressor gene has b een proposed for this CDKI. In this study we evaluated the expression of p15 by cytofluorometric, immunohistochemical, and reverse transcrip tase-polymerase chain reaction (RT-PCR) methods in CDKI. progenitors ( both during steady slate and after chemotherapy and/or granulocyte-col ony stimulating factor [C-CSF] administration) and in cells belonging to different hematopoietic differentiative lineages. We found that p15 is not expressed in normal G0/G1-arrested peripheral blood (PB)- or b one marrow (BM)-CD34(+) cells. Moreover, p15 is expressed in G0/G1-blo cked CD34(+) cells mobilized by chemotherapy and G-CSF but not in CD34 (+) cells mobilized by G-CSF alone. To clarify the role of p15 in norm al hematopoiesis, we used flow cytometry to investigate its expression in normal differentiating BM and PB cells. We found that p15 was expr essed in cells belonging to the granulocyte-monocyte lineage and in B and T lymphocytes, whereas erythroid and megakaryocytic cells were p15 negative. These findings, which were confirmed both by immunohistoche mical and RT-PCR analysis, definitely establish a linkage between p15 expression and granulocyte-monocyte differentiation.