Differences between healthy hematopoietic progenitors and leukemia cells with respect to CD44 mediated rolling versus adherence behavior on hyaluronic acid coated surfaces

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• 作者：Maximilian Hanke ; Isabel Hoffmann ; Christof Christophis ; Mario Schubert ; Van T. Hoang ; Abraham Zepeda-Moreno ; Natalia Baran ; Volker Eckstein ; Patrick Wuchter ; Axel Rosenhahn ; Anthony D. Ho
• 关键词：CD44 ; Hyaluronic acid ; Hematopoietic progenitor cell ; Acute myeloid leukemia ; Shear stress ; Rolling
• 刊名：Biomaterials
• 出版年：February, 2014
• 年：2014
• 卷：35
• 期：5
• 页码：1411-1419
• 全文大小：3459 K

文摘

We previously demonstrated that leukemia cell lines expressing CD44 and hematopoietic progenitor cells (HPC) from umbilical cord blood (CB) showed rolling on hyaluronic acid (HA)-coated surfaces under physiological shear stress. In the present study, we quantitatively assessed the interaction of HPC derived from CB, mobilized peripheral blood (mPB) and bone marrow (BM) from healthy donors, as well as primary leukemia blasts from PB and BM of patients with acute myeloid leukemia (AML) with HA. We have demonstrated that HPC derived from healthy donors showed relative homogeneous rolling and adhesion to HA. In contrast, highly diverse behavioral patterns were found for leukemia blasts under identical conditions. The monoclonal CD44 antibody (clone BU52) abrogated the shear stress-induced rolling of HPC and leukemia blasts, confirming the significance of CD44 in this context. On the other hand, the immobile adhesion of leukemia blasts to the HA-coated surface was, in some cases, not or incompletely inhibited by BU52. The latter property was associated with non-responsiveness to induction chemotherapy and subsequently poor clinical outcome.