Migratory behavior of leukemic cells from acute myeloid leukemia patients.
The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 contribute to stem cell homing and may play a role in the trafficking of leukemic cells. Therefore, we analyzed migration across Transwell filters of cells derived from bone marrow (BM) or peripheral blood (PB) from 26 acute myeloid leukemia (AML) patients. The presence of the extracellular matrix protein fibronectin (FN) strongly enhanced the spontaneous and SDF-1-induced migration of leukemic PB and BM cells. No differences in spontaneous, SDF-1-induced migration or CXCR-4 expression were observed between the different AML subtypes. Subsequently, it was determined whether SDF-1 preferentially promoted migration of subsets of leukemic cells. Leukemic cells expressing CD34, CD38 and HLA-DR were preferentially migrating, whereas cells expressing CD14 and CD36 showed diminished migration. Analysis of paired PB and BM samples indicated that significantly higher SDF-1-induced migration was observed in AML for CD34(+) BM-derived cells compared to CD34(+) PB-derived cells, suggesting a role for SDF-1 in the anchoring of leukemic cells in the BM or other organs. The lower percentage of circulating leukemic blasts in patients with a relatively high level of SDF-1-induced migration also supports this hypothesis. In conclusion, we have shown that primary AML cells are migrating towards SDF-1 independent of the AML subtypes.
Voermans
C
C
Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
van Heese
W P M
WP
de Jong
I
I
Gerritsen
W R
WR
van Der Schoot
C E
CE
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D002453:Cell Cycle; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005353:Fibronectins; D019718:Receptors, CXCR4