Journal Article

WT1 in acute leukemia, chronic myelogenous leukemia and myelodysplastic syndrome: therapeutic potential of WT1 targeted therapies

Cheever, M A, Rosenfeld, C, Gaiger, A

2003

Overview

Among clinicians, initial awareness of the Wilms' tumor gene was limited mostly to pediatric oncologists. Almost a decade ago, overexpression of Wilms' tumor 1 (WT1) was observed in adult acute leukemia. Subsequent studies indicated that WT1 overexpression occurs in most cases of acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS). Limited tissue expression of WT1 in adults suggests that WT1 can be a target for leukemia/MDS therapy. WT1 expression in stem/progenitor cells remains unsettled. However, lack of progenitor cell suppression by WT1 antisense or WT1-specific cytotoxic T cells provide some assurance that WT1 expression in progenitor cells is minimal or absent. Immunotherapy-based WT1 approaches are furthest along in preclinical development. WT1-specific cytotoxic lymphocytes can be generated from normals and leukemic patients. In mice, WT1 vaccines elicit specific immune responses without evidence of tissue damage. In this paper, we review studies validating the immunogenicity of WT1 and propose that leukemia and MDS may be a good clinical model to test the efficacy of a WT1 vaccine.

• Publisher: Nature Publishing Group
• Subject: Acute Disease / Acute lymphoblastic leukemia / Acute myeloid leukemia / Adults / Cancer Vaccines / Chronic myeloid leukemia / Cytotoxicity / Graft versus host disease / Humans / Immunogenicity / Immunotherapy / Immunotherapy - methods / Immunotherapy, Adoptive / Leukemia / Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy / Lymphatic leukemia / Lymphocytes / Lymphocytes T / Myelodysplastic syndrome / Myelodysplastic syndromes / Myelodysplastic Syndromes - therapy / Pediatrics / Polymerase chain reaction / Progenitor cells / Remission (Medicine) / Stem cells / Tumors / Vaccines / Wilms' tumor / WT1 Proteins - analysis / WT1 Proteins - antagonists & inhibitors / WT1 Proteins - immunology