This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kalinkovich, A. Articles by Lapidot, T. Search for Related Content PubMed PubMed Citation Articles by Kalinkovich, A. Articles by Lapidot, T.

Functional CXCR4-Expressing Microparticles and SDF-1 Correlate with Circulating Acute Myelogenous Leukemia Cells

¹ Department of Immunology, Weizmann Institute of Science; ² Kaplan Medical Center, Rehovot, Israel; ³ The Hematology Institute, Tel-Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; ⁴ Hematology and BMT Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel; and ⁵ Coagulation Unit and ⁶ Department of BMT and Cancer Immunotherapy, Hadassah Hebrew University Medical School, Jerusalem, Israel

Requests for reprints: Tsvee Lapidot, Department of Immunology, The Weizmann Institute of Science, P.O. Box 26, Rehovot 76100, Israel. Phone: 972-8-9342481; Fax: 972-8-934141; E-mail: Tsvee.Lapidot{at}weizmann.ac.il.

Stromal cell–derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 are implicated in the pathogenesis and prognosis of acute myelogenous leukemia (AML). Cellular microparticles, submicron vesicles shed from the plasma membrane of various cells, are also associated with human pathology. In the present study, we investigated the putative relationships between the SDF-1/CXCR4 axis and microparticles in AML. We detected CXCR4-expressing microparticles (CXCR4⁺ microparticles) in the peripheral blood and bone marrow plasma samples of normal donors and newly diagnosed adult AML patients. In samples from AML patients, levels of CXCR4⁺ microparticles and total SDF-1 were elevated compared with normal individuals. The majority of CXCR4⁺ microparticles in AML patients were CD45⁺, whereas in normal individuals, they were mostly CD41⁺. Importantly, we found a strong correlation between the levels of CXCR4⁺ microparticle and WBC count in the peripheral blood and bone marrow plasma obtained from the AML patients. Of interest, levels of functional, noncleaved SDF-1 were reduced in these patients compared with normal individuals and also strongly correlated with the WBC count. Furthermore, our data indicate NH₂-terminal truncation of the CXCR4 molecule in the microparticles of AML patients. However, such microparticles were capable of transferring the CXCR4 molecule to AML-derived HL-60 cells, enhancing their migration to SDF-1 in vitro and increasing their homing to the bone marrow of irradiated NOD/SCID/ß2m^null mice. The CXCR4 antagonist AMD3100 reduced these effects. Our findings suggest that functional CXCR4⁺ microparticles and SDF-1 are involved in the progression of AML. We propose that their levels are potentially valuable as an additional diagnostic AML variable. (Cancer Res 2006; 66(22): 11013-20)

This article has been cited by other articles:

				T. Papayannopoulou and D. T. Scadden Stem-cell ecology and stem cells in motion Blood, April 15, 2008; 111(8): 3923 - 3930. [Abstract] [Full Text] [PDF]

				C. Xu, J. Sui, H. Tao, Q. Zhu, and W. A. Marasco Human Anti-CXCR4 Antibodies Undergo VH Replacement, Exhibit Functional V-Region Sulfation, and Define CXCR4 Antigenic Heterogeneity J. Immunol., August 15, 2007; 179(4): 2408 - 2418. [Abstract] [Full Text] [PDF]