Effect Of Human Bone Marrow Fibroblastoid Stromal Cell Line HFCL On The Proliferation, Differentiation And Apoptosis Of Acute Myeloid Leukemia Cell Lines

Leukemia, which is a clonal expansion of malignant hematopoietic cells in bone marrow, blood or other tissue, is one of common cancers. Although great advances have been made in the study on pathophysiological mechanism, diagnosis and therapy of leukemia in recent 20 years, there are many problems needed to be dealed with, such as refractory and relapse leukemia, recurrence after stem cell transplantation. Previously research works were concentrated on leukemic cells themselves, but considerably less attention has been directed toward examining the role of hematopoietic microenvironment (HM) in the initiation and progression of leukemia until now. Leukemic cells, like their normal hematopoietic counterparts, are subjected to the influence of the HM. Bone marrow stromal cells (BMSCs) are the main components of HM, which can regulate the normal hematopoiesis though direct adhesion and secretion of cytokines. Recently it has been found that the encounters betweenthe BMSCs and leukemic cells affect the growth, proliferation, differentiation, trafficking and apoptosis of leukemic cells. By investigating the interaction between BMSCs and leukemic cells, new understanding of the pathogenesis, and new ideal and strategy for the therapy of leukemia will be offered.Years ago, long-term cultured BMSCs, which are the mixture of various cells, were used to study the relationship between the BMSCs and leukemic cells. So it is difficult to say which kind of BMSCs play a role in an interaction between them. At present study, different BMSCs cell lines are applied to make convenience for in vitro experiments and to be advantageous to make sure which kind of BMSCs play a more important role in this relationship. Previous studies have shown that direct interaction with stromal cells could increase the survival of B lineage acute lymphoblastic leukemia(ALL) cell lines during Ara-C or VP-16 exposure, emphasizing the role of bone marrow stromal cell Dexter-system cultures in the maintenace of B lineage leukemic disease with participation of VLA-4, 5 and VCAM-1, ICAML-1. And the protective effect of the bone marrow microenvironment on leukemic cells may be due, in part, to regulation of caspase 3 activity. But up to now, the detailed molecular mechanisms by which BMSCs affect the proliferation, differentiation and apoptosis of ALL are not clear. As for acute myeloid leukemia(AML), it has been recently reported that AML blasts undergo apoptosis when cultured in serum-free conditions and that myeloid growth factors either alone or in combination had limited abilities to decrease apoptosis and increase clonogenic potential of AML blasts. And human BMSCs have been shown to be more effective than myeloid growth factors in inhibiting apoptosis of AML blasts. In comparison to control group, direct contact with HS-5, a fibroblastoid stromal cell line significantly inhibited culture-induced and drug-induced apoptosis of AML cells. HS-5-mediated apoptosis inhibition was not consistently associated with increased bcl-2protein in AML cells. However, a later study showed that murine MS-5 stromal cells prevented apoptosis in HL-60 cells and in primary AML blasts via modulation of Bcl-2 family proteins ( Bcl-2 and Bcl-xL ). It was obvious that these results conflicted with each other. The present studies showed that BMSCs affected the survival of AML cells, but it was still unknown which components of BMSCs is the most effective, if the mechanisms of AML are similar to the one of ALL, if there are molecules associated with apoptosis and other signal transduction molecules involving in this process, and which ways are more effective, direct contact or secretion of cytokines. These are not clear to date. Consequently, the effects and mechanisms of BMSCs on the proliferation, differentiation and apoptosis of acute myeloid leukemia remain to be investigated.In this study, to investigate the effects of human bone marrow fibroblastoid stromal cell line (HFCL) on the proliferation, differentiation and apoptosis of AML sensitive U937, HL-60 cell line...