title: Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies.
abstract: Wilms tumor gene WT1 is expressed at high levels in hematopoietic malignancies, such as leukemias and myelodysplastic syndromes (MDS), and in various kinds of solid tumors, including lung cancer, and it exerts an oncogenic function in these malignancies. IgM and IgG WT1 antibodies were measured by means of dot blot assay in 73 patients with hematopoietic malignancies (16 acute myeloid leukemia [AML], 11 acute lymphoid leukemia [ALL], 13 chronic myeloid leukemia [CML], and 33 MDS) and 43 healthy volunteers. Immunoglobulin IgM, IgG, and IgM+IgG WT1 antibodies were detected in 40 (54.8%), 40 (54.8%), and 24 (32.8%), respectively, of the 73 patients with hematopoietic malignancies, whereas 7 (16.2%), 2 (4.7%), and none of the 43 healthy volunteers had IgM, IgG, or IgM+IgG WT1 antibodies, respectively. Furthermore, immunoglobulin isotype class switching of WT1 antibodies from IgM to IgG occurred in conjunction with disease progression from refractory anemia (RA) to RA with excess of blasts (RAEB), and further to RAEB in transformation (RAEB-t) in MDS patients. These results showed that humoral immune responses against the WT1 protein could be elicited in patients with WT1-expressing hematopoietic malignancies, and they suggested that the helper T-cell responses needed to induce humoral immune responses and immunoglobulin isotype class switching from IgM to IgG were also generated in these patients. Our findings may provide new insight into the rationale for elicitation of cytotoxic T-cell responses against the WT1 protein in cancer immunotherapy using the WT1 vaccine.
authors.affiliation: Department of Radiation Biology, Osaka University Medical School, Japan.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Elisseeva
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Ogata
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.forename: Eui Ho
authors.initials: EH
authors.lastname: Kim
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kubota
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yamagami
authors.forename: Akira
authors.initials: A
authors.lastname: Hiraoka
authors.forename: Machiko
authors.initials: M
authors.lastname: Tsukaguchi
authors.forename: Keiko
authors.initials: K
authors.lastname: Udaka
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Taisei
authors.initials: T
authors.lastname: Nomura
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood*; D000917:Antibody Formation / Q000502:physiology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D017578:Immunoglobulin Class Switching / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D025721:WT1 Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D000912:Antibodies, Neoplasm; D025721:WT1 Proteins