EXPRESSION OF THE LEUKEMIA-ASSOCIATED GENE, P18, IN NORMAL AND MALIGNANT-TISSUES - INACTIVATION OF EXPRESSION IN A PATIENT WITH CLEAVED B-CELL LYMPHOMA LEUKEMIA

p18 is a well conserved gene coding for an 18 kDa cytosolic phosphopro tein. Although the function of p18 is unknown, it is suspected of play ing a role in regulation of cell proliferation or the proliferation-di fferentiation switch. Here we have found p18 mRNA expression highest i n testis, brain, thymus and a multipotent hematopoietic stem cell line and lowest in liver. p18 was also expressed vigorously in all but one of 85 diverse tumor cell lines and primary human malignant specimens examined. In five primary tumors, expression was substantially elevate d with respect to expression in contiguous normal tissue. Expression i n chronic phase chronic myelogenous leukemia cells was far greater tha n in normal blood cells and increased with progression of disease. In liver material, the highest level of p18 was found in a primary hepato blastoma, a stem cell tumor, whereas a benign adenoma demonstrated ver y low level expression. Cells from a cleaved B cell lymphoma/leukemia failed to express p18 whereas 18 specimens from other B lymphoid malig nancies, including a second cleaved cell malignancy, expressed p18 at substantial levels. These data are consistent with p18 playing a role in control of cell proliferation in at least certain tissues. The ques tions arise if high level p18 expression in certain malignancies may p lay a primary role in driving cell proliferation or, based on chromoso mal localization and inactivation of p18 expression in one lymphoma, i f p18 may act as a tumor suppressor.