Expression of the chemokine receptors CXCR4 and CCR7 and, disease progression in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma

被引:64
作者
Ghobrial, IM
Bone, ND
Stenson, MJ
Novak, A
Hedin, KE
Kay, NE
Ansell, SM
机构
[1] Mayo Clin, Coll Med, Div Hematol & Internal Med, Rochester, MI USA
[2] Mayo Clin, Coll Med, Transport Biol Unit, Dept Surg, Rochester, MI USA
[3] Mayo Clin, Coll Med, Dept Immunol, Rochester, MI USA
关键词
D O I
10.4065/79.3.318
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL). Patients and Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons. The patients were treated at the Mayo Clinic in Rochester, Minn, between January 15,1991, and February 7, 2003. Mononuclear cells were stained by a 2-color (fluorescein isothiocyanate/phycoerythrin) flow cytometric assay using antibodies to the chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CCR2, CCR4, CCR5, CCR6, and CCR7) and also to CD19. Results: Of the 45 patients in this study,,20 had Rai stage 0 disease, 12 had stage I disease, 3 had stage II disease, 2 had stage III disease, and 8 had stage IV disease. The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P=.003) and CCR7 (P=.001) on B-CLL cells. We also found a significant increase in the expression of CXCR4 and CCR7 in B-CLL cells from patients with stage IV compared with stage 0 disease (P=.001 and P=.02, respectively). Furthermore, circulating B-CLL cells showed significantly higher expression of CXCR4 and CCR7 when compared with B lymphocytes in lymph nodes (P=.003 and. P<.001, respectively). Conclusion: The expression of CXCR4 and CCR7 on B-CLL cells correlates with Rai stage. Also, these chemo kine receptors may be down-regulated once malignant B cells enter the lymph nodes. To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells.
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页码:318 / 325
页数:8
相关论文
共 37 条
[1]   CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease [J].
Barretina, J ;
Juncà, J ;
Llano, A ;
Gutiérrez, A ;
Flores, A ;
Blanco, J ;
Clotet, B ;
Esté, JA .
ANNALS OF HEMATOLOGY, 2003, 82 (08) :500-505
[2]   B lymphocyte chemotaxis regulated in association with microanatomic localization, differentiation state, and B cell receptor engagement [J].
Bleul, CC ;
Schultze, JL ;
Springer, TA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (05) :753-762
[3]   Developmental switches in chemokine response profiles during B cell differentiation and maturation [J].
Bowman, EP ;
Campbell, JJ ;
Soler, D ;
Dong, ZJ ;
Manlongat, N ;
Picarella, D ;
Hardy, RR ;
Butcher, EC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (08) :1303-1317
[4]  
Burger JA, 2000, BLOOD, V96, P2655
[5]   Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells [J].
Burger, JA ;
Burger, M ;
Kipps, TJ .
BLOOD, 1999, 94 (11) :3658-3667
[6]   Chemokine receptors and stromal cells in the homing and homeostasis of chronic lymphocytic leukemia B cells [J].
Burger, JA ;
Kipps, TJ .
LEUKEMIA & LYMPHOMA, 2002, 43 (03) :461-466
[7]   Lymphocyte homing and homeostasis [J].
Butcher, EC ;
Picker, LJ .
SCIENCE, 1996, 272 (5258) :60-66
[8]   Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia [J].
Damle, RN ;
Wasil, T ;
Fais, F ;
Ghiotto, F ;
Valetto, A ;
Allen, SL ;
Buchbinder, A ;
Budman, D ;
Dittmar, K ;
Kolitz, J ;
Lichtman, SM ;
Schulman, P ;
Vinciguerra, VP ;
Rai, KR ;
Ferrarini, M ;
Chiorazzi, N .
BLOOD, 1999, 94 (06) :1840-1847
[9]   Differential expression of chemokine receptors in B cell malignancies [J].
Dürig, J ;
Schmücker, U ;
Dührsen, U .
LEUKEMIA, 2001, 15 (05) :752-756
[10]   CHRONIC LYMPHOCYTIC-LEUKEMIA - AN UPDATED REVIEW [J].
FAGUET, GB .
JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (09) :1974-1990