Hardy C L, Omoto E, Tavassoli M
Department of Veterans Affairs Medical Center, Jackson, Miss.
Pathobiology. 1990;58(3):179-84. doi: 10.1159/000163580.
Selective homing of hemopoietic progenitor cells to hemopoietic organs is the initial event in hemopoiesis. At a molecular level, it is mediated by a membrane receptor on the surface of hemopoietic progenitor cells. The receptor molecule then binds selectively to a glycoconjugate on the surface of bone marrow stromal cells. The molecular nature of this receptor has been shown previously to be a lectin with specificity for an as yet unknown configuration of galactosyl and mannosyl residues of the glycoconjugate. Normal murine progenitor cell lines, FDCP-1 and B6SUT, were found to possess this homing receptor on their cell membrane, and they also bind well to hemopoietic stroma. However, when three human leukemic cell lines, U937, HL60 and K562, were probed for the presence of this receptor, they were found to be deficient in the homing protein. Further, these cells showed little ability to bind the hemopoietic stromal cell line, GB1/6. These findings suggest that leukemic cells experience a loss, or at least alteration, of homing receptor molecule during leukemic transformation. This can result in a diminished ability to bind to marrow stroma. The lack of homing function may be of pathogenetic significance in the lack of differentiation of leukemic cells and may also contribute to the dissemination of leukemic cells in the circulation.
造血祖细胞向造血器官的选择性归巢是造血过程中的初始事件。在分子水平上,它由造血祖细胞表面的膜受体介导。然后,该受体分子选择性地与骨髓基质细胞表面的糖缀合物结合。先前已证明该受体的分子性质是一种凝集素,对糖缀合物中半乳糖基和甘露糖基残基的一种尚不清楚的构型具有特异性。发现正常小鼠祖细胞系FDCP - 1和B6SUT在其细胞膜上具有这种归巢受体,并且它们也能很好地与造血基质结合。然而,当检测三种人类白血病细胞系U937、HL60和K562是否存在这种受体时,发现它们缺乏归巢蛋白。此外,这些细胞与造血基质细胞系GB1/6的结合能力很弱。这些发现表明,白血病细胞在白血病转化过程中经历了归巢受体分子的丢失或至少是改变。这可能导致与骨髓基质结合的能力减弱。归巢功能的缺乏可能在白血病细胞缺乏分化方面具有致病意义,也可能有助于白血病细胞在循环中的播散。