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


METHODS
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 CML blast crisis but barely detectable in normal bone marrow, normal peripheral blood, or leukemic cells from patients with stable-phase CML. In contrast, purified CD34+ progenitors from normal individuals and patients with stable-phase CML 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 CML 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 CML.
Wu
Catherine J
CJ
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. CWU@PARTNERS.ORG
Biernacki
Melinda
M
Kutok
Jeffery L
JL
Rogers
Shelby
S
Chen
Linyun
L
Yang
Xiao-Feng
XF
Soiffer
Robert J
RJ
Ritz
Jerome
J
D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; D015972:Gene Expression Regulation, Neoplastic; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D023461:Myeloid Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C467564:EXOSC5 protein, human; C431278:NUDCD1 protein, human; D016601:RNA-Binding Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex