Graft-versus-leukemia target antigens in chronic myelogenous leukemia are expressed on myeloid progenitor cells

被引:46
作者
Wu, CJ
Biernacki, M
Kutok, JL
Rogers, S
Chen, LY
Yang, XF
Soiffer, RJ
Ritz, J
机构
[1] Dana Farber Canc Inst, Div Hematol Malignacies, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
D O I
10.1158/1078-0432.CCR-05-0036
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Donor lymphocyte infusion (DLI) reliably induces durable remission in 75% to 80% of patients with relapsed chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation. We previously reported the identification of a high titer - specific immunoglobulin G response against two novel leukemia-associated antigens, CML28 and CML66, which correlated with immune-induced remission. The present studies characterize expression of CML28 and CML66 in primary hematopoietic tissues. Experimental Design: Specific monoclonal antibodies to CML28 and CML66 were developed and used to detect antigen expression in leukemia cell lines and primary leukemia tissue on Western blot and immunohistochemistry. Expression patterns were confirmed by antigen-specific real-time PCR. Results: Both CML28 and CML66 were highly expressed in leukemic blasts from patients with acute myelogenous leukemia and CIVIL blast crisis but barely detectable in normal bone marrow, normal peripheral blood, or leukemic cells from patients with stable-phase CIVIL. In contrast, purified CD34(+) progenitors from normal individuals and patients with stable-phase CIVIL expressed high levels of CML28 and CML66 transcript and protein. Immunohistochemical staining for CML66 confirmed rare staining of myeloid precursors in normal marrow and diffuse staining of myeloblastic cells in acute myelogenous leukemia and blast crisis CIVIL marrows. Conclusions: The expression patterns of CML28 and CML66 are strikingly similar and suggest that antigen expression may play a role in shaping the post-DLI antibody repertoire. The CD34(+) restricted pattern of expression of CML28 and CML66 is particularly relevant in light of the notion that DLI likely exerts its curative effect by targeting antigens present in self-renewing malignant progenitor populations in CIVIL.
引用
收藏
页码:4504 / 4511
页数:8
相关论文
共 45 条
[1]   Toxicity and efficacy of defined doses of CD4+ donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant [J].
Alyea, EP ;
Soiffer, RJ ;
Canning, C ;
Neuberg, D ;
Schlossman, R ;
Pickett, C ;
Collins, H ;
Wang, YL ;
Anderson, KC ;
Ritz, J .
BLOOD, 1998, 91 (10) :3671-3680
[2]   Fcγ receptors and cross-presentation in dendritic cells [J].
Amigorena, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (01) :F1-F3
[3]   Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens [J].
Bellucci, R ;
Wu, CJ ;
Chiaretti, S ;
Weller, E ;
Davies, FE ;
Alyea, EP ;
Dranoff, G ;
Anderson, KC ;
Munshi, NC ;
Ritz, J .
BLOOD, 2004, 103 (02) :656-663
[4]  
BELLUCCI R, 2005, BLOOD 0203
[5]   DIFFERENCES IN THE FREQUENCY OF NORMAL AND CLONAL PRECURSORS OF COLONY-FORMING CELLS IN CHRONIC MYELOGENOUS LEUKEMIA AND ACUTE MYELOGENOUS LEUKEMIA [J].
BERNSTEIN, ID ;
SINGER, JW ;
SMITH, FO ;
ANDREWS, RG ;
FLOWERS, DA ;
PETERSENS, J ;
STEINMANN, L ;
NAJFELD, V ;
SAVAGE, D ;
FRUCHTMAN, S ;
ARLIN, Z ;
FIALKOW, PJ .
BLOOD, 1992, 79 (07) :1811-1816
[6]   CD8+ minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells [J].
Bonnett, D ;
Warren, EH ;
Greenberg, PD ;
Dick, JE ;
Riddell, SR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (15) :8639-8644
[7]   Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3′ end formation [J].
Briggs, MW ;
Burkard, KTD ;
Butler, JS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) :13255-13263
[8]   Autoantibodies directed to novel components of the PM/Scl complex, the human exosome [J].
Brouwer, R ;
Egberts, WTV ;
Hengstman, GJD ;
Raijmakers, R ;
van Engelen, BGM ;
Seelig, HP ;
Renz, M ;
Mierau, R ;
Genth, E ;
Pruijn, GJM ;
van Venrooij, WJ .
ARTHRITIS RESEARCH, 2002, 4 (02) :134-138
[9]   The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma [J].
Brouwer, R ;
Pruijn, GJM ;
van Venrooij, WJ .
ARTHRITIS RESEARCH, 2001, 3 (02) :102-106
[10]   Cytokine-regulated expression of survivin in myeloid leukemia [J].
Carter, BZ ;
Milella, M ;
Altieri, DC ;
Andreeff, M .
BLOOD, 2001, 97 (09) :2784-2790