DOI: 10.1046/j.1365-2141.2000.02157.x. Functional response of leukaemic blasts to stromal cell‐derived factor‐1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia

Functional response of leukaemic blasts to stromal cell‐derived factor‐1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia

10.1046/j.1365-2141.2000.02157.x

Crossref journal-article

Wiley

British Journal of Haematology (311)

Abstract

The chemokine stromal cell‐derived factor‐1 (SDF‐1) that is released by bone marrow (BM) stromal cells and contributes to stem cell homing may also play a role in the trafficking of leukaemic cells. We analysed SDF‐1‐induced intracellular calcium fluxes in leukaemic blasts from the peripheral blood of patients with newly diagnosed acute myeloid leukaemia (AML) and lymphoblastic leukaemia (B‐lineage ALL), determined the effect of BM stromal cell‐conditioned medium on in vitro transendothelial migration (TM) and measured expression of the SDF‐1 receptor, CXCR4, by flow cytometry. AML FAB M1/2 blasts did not show calcium fluxes and TM was not stimulated. In myelomonocytic AML (M4/5), however, SDF‐1 induced significant calcium fluxes and TM was increased twofold by the conditioned medium. M3 and M4 blasts with eosinophilia (M4eo) showed intermediate activity and M6 blasts showed no functional activity. In ALL, strong calcium fluxes and increased TM (2.5‐fold) were observed. Accordingly, expression of CXCR4 was low in undifferentiated (M0) AML, myeloid (M1/2) AML and erythroid (M6) AML, but high [mean fluorescence (MF) > 50] in promyelocytic (M3) AML, myelomonocytic (M4/5) AML and B‐lineage ALL. We conclude that, in AML, SDF‐1 is preferentially active in myelomonocytic blasts as a result of differentiation‐related expression of CXCR4. Functional activity of SDF‐1 and high expression of CXCR4 in B‐lineage ALL is in accordance with the previously described activity of SDF‐1 in early B cells. SDF‐1 may contribute to leukaemic marrow infiltration, as suggested by increased CXCR4 expression and migratory response in BM‐derived blasts compared with circulating cells.

Bibliography

MÃ¶hle, R., Schittenhelm, M., Failenschmid, C., Bautz, F., KratzâAlbers, K., Serve, H., Brugger, W., & Kanz, L. (2000). Functional response of leukaemic blasts to stromal cellâderived factorâ1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia. British Journal of Haematology, 110(3), 563â572. Portico.

Authors 8

Robert Möhle (first)
Marcus Schittenhelm (additional)
Cornelia Failenschmid (additional)
Frank Bautz (additional)
Karsten Kratz‐Albers (additional)
Hubert Serve (additional)
Wolfram Brugger (additional)
Lothar Kanz (additional)

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Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 1:27 a.m.)
Deposited	1 year, 9 months ago (Oct. 29, 2023, 5:12 a.m.)
Indexed	1 month ago (July 24, 2025, 7:19 a.m.)
Issued	24 years, 11 months ago (Sept. 1, 2000)
Published	24 years, 11 months ago (Sept. 1, 2000)
Published Online	23 years, 8 months ago (Dec. 24, 2001)
Published Print	24 years, 11 months ago (Sept. 1, 2000)

Funders 0

None

BibTeX

@article{M_hle_2000, title={Functional response of leukaemic blasts to stromal cell‐derived factor‐1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia}, volume={110}, ISSN={1365-2141}, url={http://dx.doi.org/10.1046/j.1365-2141.2000.02157.x}, DOI={10.1046/j.1365-2141.2000.02157.x}, number={3}, journal={British Journal of Haematology}, publisher={Wiley}, author={Möhle, Robert and Schittenhelm, Marcus and Failenschmid, Cornelia and Bautz, Frank and Kratz‐Albers, Karsten and Serve, Hubert and Brugger, Wolfram and Kanz, Lothar}, year={2000}, month=sep, pages={563–572} }

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