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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2003 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00155844
First received: September 9, 2005
Last updated: NA
Last verified: January 2003
History: No changes posted
  Purpose

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.


Condition
Acute Myelocytic Leukemia
Acute Lymphocytic Leukemia

Study Type: Observational
Study Design: Observational Model: Case Control
Primary Purpose: Screening
Time Perspective: Cross-Sectional

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Estimated Enrollment: 30
Study Start Date: February 2003
Estimated Study Completion Date: July 2004
Detailed Description:

Bone marrow consists of a complex hematopoietic cellular component that continuously goes through self-replication and/or 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 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. 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. Therefore,we 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 leukemia;2). Study on the molecular mechanism for the blockade of CXCR4-CXCL12 signaling in CXCR4 (+) and SDF response (-) cells;3). Evaluate the marrow plasma and peripheral plasma to find out plasma factors that interfering the migration behavior of leukemic CXCR4 (+) but CXCL12 response (-) cells

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • acute leukemia

Exclusion Criteria:

  • nil
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00155844

Contacts
Contact: Liang-In Lin, PhD 886-2-23810611 lilin@ha.mc.ntu.edu.tw

Locations
Taiwan
Liang-In Lin Recruiting
Taipei, Taiwan
Contact: Liang-In Lin, PhD    886-2-23810611    lilin@ha.mc.ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Liang-In Lin, PhD Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00155844     History of Changes
Other Study ID Numbers: 9200200606
Study First Received: September 9, 2005
Last Updated: September 9, 2005
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014