TEL-AML1 fusion precedes differentiation to pre-B cells in childhood acute lymphoblastic leukemia
Copyright policy )TEL-AML1 fusion precedes differentiation to pre-B cells in childhood acute lymphoblastic leukemia
The TEL-AML1 gene fusion results from a karyotypically cryptic t(12;21) translocation, the most common genetic abnormality in pediatric acute lymphoblastic leukemia (ALL). The presence of the TEL-AML1 fusion in utero, its protracted latency to overt leukemia, and secondary loss of the untranslocated TEL suggest it is an initiating event. Sequences of the TEL-AML1 genomic breakpoint and the immunoglobulin heavy chain (IgH) and/or T-cell receptor (TCR) gene rearrangements were characterized in four pediatric pre-B ALL patients. Analysis of these markers in relapsed patients revealed that immunophenotypically and cytogenetically distinct, and clonally unrelated antigen receptor leukemic cell populations harbored the same initiating TEL-AML1 molecular abnormality. Furthermore, TEL-AML1-positive cells persisted during remission even in the absence of detectable clone-specific IgH and TCR markers. We demonstrate that the TEL-AML1 translocation can occur in vivo during B-cell development before rearrangement of the IgH and TCR genes. We propose, in some cases, that the TEL-AML1 translocation occurs in a stem or B progenitor cell, and that recurrent TEL-AML1-positive pre-B ALL represents a de novo-transformed population that retains the same diagnostic initiating event.
- University of California, San Francisco United States
- University of California System United States
- New York Medical College United States
Male, B-Lymphocytes, Neoplasm, Residual, Adolescent, Base Sequence, Oncogene Proteins, Fusion, Molecular Sequence Data, Cell Differentiation, Chromosome Breakage, Clone Cells, Immunophenotyping, Genes, T-Cell Receptor, Cell Transformation, Neoplastic, Chronology as Topic, Child, Preschool, Core Binding Factor Alpha 2 Subunit, Humans, Female, Child, Immunoglobulin Heavy Chains
Male, B-Lymphocytes, Neoplasm, Residual, Adolescent, Base Sequence, Oncogene Proteins, Fusion, Molecular Sequence Data, Cell Differentiation, Chromosome Breakage, Clone Cells, Immunophenotyping, Genes, T-Cell Receptor, Cell Transformation, Neoplastic, Chronology as Topic, Child, Preschool, Core Binding Factor Alpha 2 Subunit, Humans, Female, Child, Immunoglobulin Heavy Chains
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