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  • Title: Expression of B cell-associated transcription factors in B-cell precursor acute lymphoblastic leukemia cells: association with PU.1 expression, phenotype, and immunogenotype.
    Author: Nishii K, Kita K, Miwa H, Shikami M, Taniguchi M, Usui E, Katayama N, Shiku H.
    Journal: Int J Hematol; 2000 Jun; 71(4):372-8. PubMed ID: 10905058.
    Abstract:
    B-lymphocyte development progresses through discrete stages characterized by regular DNA rearrangements of the immunoglobulin (Ig) loci that lead to the transcription of Ig genes and expression of B-cell antigen receptors. These developmental processes can also be distinguished by the expression of specific cell-surface markers. Therefore, rearrangement of the Ig, T-cell receptor (TCR) genes, and surface markers are generally considered as useful markers of the B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangement of Ig and TCR genes (double genotype) has been reported in the most immature lymphoid malignancies (lineage promiscuity), mainly in B-cell precursor acute lymphoblastic leukemia (pre-B ALL), but the mechanism is not fully understood. DNA rearrangements and specific cell-surface markers are regulated by several specific transcription factors. To better characterize the lineage promiscuity, we studied the relationship among the expression of lymphoid-associated transcription factors, phenotype, and immunogenotype. Rearrangement of the Ig light chain kappa gene was found in 37% of pre-B ALL samples and in all B-cell chronic lymphocytic leukemia (B-CLL) samples. Rearrangement of TCR gamma gene was shown in 40% of pre-B ALL samples but was not detected in any of the B-CLL samples. Among the tested B cell-associated transcription factors, Pax5 and E47 genes were expressed in all pre-B ALL and B-CLL samples. RAG-1 gene was expressed in all pre-B ALL samples but not in the B-CLL samples. Oct-2 gene was expressed in 82% of pre-B ALL and all B-CLL samples. The expression of PU.1 gene was shown in 56% of pre-B ALL but not in the B-CLL samples. Interestingly, the samples of pre-B ALL, which did not express the PU.1 gene, showed a significantly high frequency of TCR gamma gene rearrangement. This phenomenon was not found with Oct-2 gene expression. These findings suggest that absence of PU.1 expression may result in lineage promiscuity, such as the simultaneous rearrangements of Ig and TCR genes in pre-B ALL cells.
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