Studies on the Significance of CXCR4-CXCL12 on Leukemic Cells Passing Through"Marrow-Blood Barrier"

Bone marrow consists of a complex hematopoietic cellular component.When the blood progenitor cells differentiate to mature cells, they will exit unassisted to peripheral blood. On the other hand, the immature cells trapped by marrow-blood barrier. However, malignant transformation of the hematopoietic progenitor cells in AML and CML results in a blockade of their ability to terminally differentiate, causing a rapid accumulation of immature cells.Chemokines have been shown to direct the movement of cells between intravascular and extravascular compartments.The CXC chemokine CXCL12, the ligand of CXCR4, activates distinct signaling pathways that may mediate cell migration.In the preliminary research, we analyze the CXCR4 expression and the chemotactic response of CXCL12 and peripheral plasma in six leukemia cell lines (HL-60, HL-CZ, K562, U937, Raji and Jurkat) and found that three categories among them could be suggested: one is CXCR4 (-) and CXCL12 response (-), such as HL-CZ and K562 cells; the other is CXCR4 (+) and CXCL12 response (-), such as HL-60 and Raji cells; the rest is CXCR4 (+) and CXCL12 response (+), such as Jurkat and U937 cells. These results make us wonder that the leukemic cells could egress to PB from BM is due to destruction of homing process or the activation of mobilization process through CXCR4-CXCL12 axis dysfunction. Therefore,we will focus on evaluating the mechanism of CXCR4-CXCL12 axis dysfunction in the various leukemic cell lines and primary leukemic cells.