Differential expression of lymphoid and myeloid markers on differentiatinghematopoietic stem cells in normal and tumor-bearing adult human liver

The presence and phenotype of lineage-committed hematopoietic progenitors i n the normal adult human liver (AHL) were investigated and compared with th e profiles of differentiating hematopoietic precursor populations detected in liver bearing metastases of colonic origin. Levels of hematopoietic stem cells (HSCs) (CD34(+)CD45(+)) detected in hepatic mononuclear cell (HMNC) populations were increased 6-fold when compared with matched peripheral blo od samples. In normal liver, less than 5% of HSCs expressed the myeloid-ass ociated antigen, CD33, whereas considerable proportions expressed lymphoid- associated markers (T cell, 33.39%; B cell, 17.39%; and natural killer [NK] cell, 37.17%). Significant increases were observed in the relative proport ions of hepatic HSCs coexpressing CD33 (20.53%; P = .001), and the T-cell m arker (CD7, 58.13%; P = .02) in tumor-bearing liver compared with normal li ver. HSCs with B-cell progenitor phenotype (CD19(+)) were significantly dec reased in tumor-bearing liver (0.06%; P = .02). Despite these differences, the activation status of hematopoiesis, as measured by the coexpression of the differentiation and activation markers, CD38 and CD45RA, did not differ significantly between normal and tumor-bearing liver. These results indica te that the normal AHL harbors lineage-committed hematopoietic progenitors, and the vast majority of these progenitors express lymphoid-associated ant igens with changes occurring in both the myeloid and lymphoid compartments of the hepatic hematopoietic pathway on tumor challenge. While tumor-bearin g livers are enriched for intrahepatic myeloid precursors and T-cell progen itor cells, further studies are required to establish the origin and in sit u development potential of hepatic HSCs in the adult human and their role i n tumor immunity.