Potential to target dysregulated interleukin-2 receptor expression in canine lymphoid and hematopoietic malignancies as a model for human cancer

被引:20
作者
Dickerson, KB
Fosmire, S
Padilla, ML
Modiano, JF
Helfand, SC
机构
[1] Univ Wisconsin, Sch Vet Med, Dept Med Sci, Madison, WI 53706 USA
[2] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA
[3] Ctr Canc Causat & Prevent, AMC Canc Res Ctr, Denver, CO USA
[4] Univ Colorado, Ctr Canc, Denver, CO 80262 USA
来源
JOURNAL OF IMMUNOTHERAPY | 2002年 / 25卷 / 01期
关键词
lymphonla; leukemia; interleukin-2 receptor alpha-receptor-targeting;
D O I
10.1097/00002371-200201000-00004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lymphohematopoietic malignancies are common spontaneous diseases of dogs whose clinical presentation and biologic behavior closely resemble their human counterparts. The goal of this study was to define the potential to use canine lymphoma and leukemia as suitable models to refine therapeutic approaches targeting the interleukin-2 receptor (IL-2R). The authors evaluated the patterns of IL-2R expression in 13 dogs with multicentric non-Hodgkin's lymphoma (NHL) and in six dogs with leukemia (acute lymphocytic leukemia, n = 3; chronic lymphocytic leukemia in blast crisis, n = 1; acute monoblastic leukemia, n = 2). The authors first cloned and sequenced the complete coding domains of the wild-type canine IL-2R alpha-chain gene. They next used qualitative reverse transcription polymerase chain reaction (RT-PCR) analysis to examine IL-2R alpha, beta, and gamma(c) subunit expression in the tumors. Messenger RNA (mRNA) for the interleukin-2 receptor alpha, beta, and gamma(c) subunits that comprise the high-affinity receptor was present in samples from all dogs with NHL. Expression of functional surface IL-2R also was observed flow cytometrically in NHL cells from all four dogs tested. Leukemic cells from one dog with B cell acute lymphocytic leukemia and two dogs with acute monoblastic leukemia expressed mRNA for all three subunits, whereas cells from another dog with B cell leukemia and both dogs with T cell leukemia expressed only mRNA for the beta and gamma(c) subunits that comprise the intermediate-affinity receptor. These results indicate that the IL-2R is commonly expressed in canine lymphohematopoietic malignancies, and support the suitability of this large-animal model to evaluate targeted IL-2R cancer therapy using approaches of interest in the treatment of humans with hemolymphatic cancers.
引用
收藏
页码:36 / 45
页数:10
相关论文
共 52 条
  • [1] SERUM SOLUBLE INTERLEUKIN-2 RECEPTOR LEVELS ARE ASSOCIATED WITH CLINICAL-DISEASE STATUS AND HISTOPATHOLOGICAL GRADE IN NON-HODGKIN LYMPHOMA AND CHRONIC LYMPHOCYTIC-LEUKEMIA
    BARAK, V
    GINZBURG, M
    KALICKMAN, I
    POLLIACK, A
    [J]. LEUKEMIA & LYMPHOMA, 1992, 7 (5-6) : 431 - 438
  • [2] Barth S, 2000, INT J CANCER, V86, P718, DOI 10.1002/(SICI)1097-0215(20000601)86:5<718::AID-IJC18>3.0.CO
  • [3] 2-N
  • [4] BENNETT JM, 1985, ANN INTERN MED, V103, P626
  • [5] CARROLL SF, 1987, J BIOL CHEM, V262, P8707
  • [6] CARTER RF, 1986, CAN J VET RES, V50, P154
  • [7] CHANG MP, 1989, J BIOL CHEM, V264, P15261
  • [8] FERNANDES PJ, IN PRESS VET CLIN PA
  • [9] Frankel AE, 2000, CLIN CANCER RES, V6, P326
  • [10] IMMUNOLOGICAL MARKERS IN NON-HODGKINS-LYMPHOMA
    FREEDMAN, AS
    NADLER, LM
    [J]. HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 1991, 5 (05) : 871 - 889