Non-DNA-binding Ikaros isoform gene expressed in adult B-precursor acute lymphoblastic leukemia
- 1 July 2002
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 16 (7), 1285-1292
- https://doi.org/10.1038/sj.leu.2402533
Abstract
Ikaros, a zinc finger transcription factor, is essential for lymphoid development. Mutant mice expressing dominant-negative Ikaros gene (Ikaros) isoforms develop an aggressive form of lymphoid malignancies. We examined the expression of Ikaros isoforms in 11 leukemic cell lines and adult acute lymphoblastic leukemia cells from 36 patients with B-precursor acute lymphoblastic leukemia (pre-B ALL) and nine with T-precursor acute lymphoblastic leukemia (pre-T ALL), using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. In one pre-B ALL cell line, INC cells, and primary leukemic cells from 16 patients with pre-B ALL, we found the predominant expression of a non-DNA-binding Ikaros isoform, Ik-6. However, Ik-6 was not detected in pre-T ALL cells. All of pre-B ALL cells expressing Ik-6 were CD10+, whereas CD10− pre-B ALL cells did not express Ik-6. The expression of Ik-6 was not related to karyotype abnormalities such as t(9;22) and t(4;11). Proteins from the cells that expressed Ik-6 alone failed to bind to the Ikaros protein-specific binding sequence in DNA. Ikaros proteins lacking the DNA binding sequences were detected in the cytoplasm but not in the nucleus of the cells. When INC and primary pre-B ALL cells that express Ik-6 alone were irradiated and cultured in the absence of serum, these cells produced functional Ikaros isoforms, Ik-1 and Ik-2. Purified CD19+ CD10− and CD19+ CD10+ cells from normal human bone marrow did not express Ik-6. The predominant expression of Ik-6, which is the result of post-transcription dysregulation, is characteristic of adult pre-B ALL, especially CD10+ pre-B ALL.Keywords
This publication has 24 references indexed in Scilit:
- Molecular genetics, natural history and the demise of childhood leukaemiaEuropean Journal Of Cancer, 1999
- A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphomaCell, 1995
- Failure of B-cell differentiation in mice lacking the transcription factor EBFNature, 1995
- Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAPCell, 1994
- The helix-loop-helix gene E2A is required for B cell formationCell, 1994
- The ikaros gene is required for the development of all lymphoid lineagesCell, 1994
- Requirement of Transcription Factor PU.1 in the Development of Multiple Hematopoietic LineagesScience, 1994
- Ikaros, an Early Lymphoid-Specific Transcription Factor and a Putative Mediator for T Cell CommitmentScience, 1992
- RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangementCell, 1992
- RAG-1-deficient mice have no mature B and T lymphocytesCell, 1992