Ignite Creation Date:
2024-05-05 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00155844
Status:
UNKNOWN
Last Update Posted:
2005-09-12
First Post:
2005-09-09
Brief Title:
Studies on the Significance of CXCR4-CXCL12 on Leukemic Cells Passing ThroughMarrow-Blood Barrier
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
None
Status:
UNKNOWN
Status Verified Date:
2003-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Bone marrow consists of a complex hematopoietic cellular componentWhen 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 cellsChemokines have been shown to direct the movement of cells between intravascular and extravascular compartmentsThe CXC chemokine CXCL12 the ligand of CXCR4 activates distinct signaling pathways that may mediate cell migrationIn 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 Thereforewe will focus on evaluating the mechanism of CXCR4-CXCL12 axis dysfunction in the various leukemic cell lines and primary leukemic cells
Detailed Description:
Bone marrow consists of a complex hematopoietic cellular component that continuously goes through self-replication andor differentiation processes 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 cellsChemokines have been shown to direct the movement of cells between intravascular and extravascular compartmentsThe CXC chemokine CXCL12 the ligand of CXCR4 activates distinct signaling pathways that may mediate cell migration Recent reports demonstrated that the migration of HPC after transplantation from PB to BM via concentration gradients created by CXCL12 produced by marrow stromal cells has been proposed as integral to the homing process The mirror image of homing is mobilization of HPC from the BM to PB which in a clinical setting is induced by administration of various stimuli including hematopoietic growth factors The CXCR4-CXCL12 axis is reported to be very important in retaining the immature cells in the appropriate bone marrow compartment 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 by flow cytometry and two-chamber migration assay respectively 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 Thereforewe will focus on evaluating the mechanism of CXCR4-CXCL12 axis dysfunction in the various leukemic cell lines and primary leukemic cells from several aspects 1 Evaluate the CXCR4 expression and the CXCL12 response of leukemic cells from patients with acute leukemia2 Study on the molecular mechanism for the blockade of CXCR4-CXCL12 signaling in CXCR4 and SDF response - cells3 Evaluate the marrow plasma and peripheral plasma to find out plasma factors that interfering the migration behavior of leukemic CXCR4 but CXCL12 response - cells
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None