The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study
| Autor: | Linda D. Cooley, J J Shuster, Stephen J. Lauer, Donald H. Mahoney, M J Vuchich, Bruce M. Camitta, D. J. Pullen, Mark L. Bernstein, A T Look, V M Whitehead, C Payment |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Cancer Research Oncogene Proteins Fusion medicine.drug_class Chromosomal translocation Biology Antimetabolite Translocation Genetic hemic and lymphatic diseases Acute lymphocytic leukemia Precursor B-Cell Lymphoblastic Leukemia-Lymphoma medicine Humans Lymphocytes Progenitor cell Child neoplasms Ploidies medicine.diagnostic_test Lymphoblast Infant hemic and immune systems Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Molecular biology Methotrexate Oncology Polyglutamic Acid Child Preschool Immunology Core Binding Factor Alpha 2 Subunit Female Hyperdiploidy Fluorescence in situ hybridization medicine.drug |
| Zdroj: | Leukemia. 15(7) |
| ISSN: | 0887-6924 |
| Popis: | Lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia (BpALL) with chromosomal hyperdiploidy and with translocations affecting chromosome 12p11-13, accumulate high and low levels of methotrexate polyglutamates (MTXPGs), respectively. Recently a cryptic translocation, t(12;21) (p13;q22), has been demonstrated by molecular and fluorescence in situ hybridization techniques in this disease. The chimeric TEL-AML1 transcript, which has been associated with this translocation, can be detected in up to 25% of children with BpALL. We detected the TEL-AML1 and/or the AML1-TEL transcript in 30 (33%) of 91 patients studied. Levels of lymphoblast MTXPGs were lower in those with than in those without the TEL-AML1 translocation (P = 0.004). Hyperdiploidy was rare in lymphoblasts with the TEL-AML1 translocation (P = 0.047). Both ploidy (P= 0.0015) and TEL-AML1 status (P= 0.0043) were independently and significantly correlated with the log of the lymphoblast MTXPG level. However, the presence of TEL-AML1 or of hyperdiploidy accounted for only 22% of the variation of this value. Our results imply that each of 1.16 > or = DI and the presence of the TEL-AML1 translocation confers a 50% decrease in lymphoblast MTXPG level. When planning reduction of therapy for either of the two excellent outcome categories of hyperdiploid or TEL-AML1 BpALL, one should consider the difference between these two subgroups in the ability of lymphoblasts to accumulate MTXPGs. |
| Databáze: | OpenAIRE |
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