Abstract
We found a marked variation in BCL-2 oncoprotein expression levels of primary leukemic cells from 338 children with newly diagnosed acute lymphoblastic leukemia (ALL). None of the high-risk features predictive of poor treatment outcome in childhood ALL, such as older age, high white blood cell (WBC) count, organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression. Overall, high BCL-2 levels were not associated with slow early response, failure to achieve complete remission, or poor event-free survival. High BCL-2 levels in primary leukemic cells predicted slow early response only in T-lineage ALL patients, which comprised approximately 15% of the total patient population. Even for this small subset of patients, the level of BCL-2 expression did not have a significant impact on the short-term event-free survival.
MeSH terms
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Adolescent
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Adult
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Animals
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Apoptosis*
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Biomarkers, Tumor
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Burkitt Lymphoma / genetics
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Burkitt Lymphoma / metabolism
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Burkitt Lymphoma / mortality
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Burkitt Lymphoma / pathology
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Child
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Child, Preschool
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Cohort Studies
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Disease-Free Survival
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Female
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Gene Expression Regulation, Leukemic*
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Genes, bcl-2
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Humans
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Immunophenotyping
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Infant
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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Leukemia-Lymphoma, Adult T-Cell / mortality
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Male
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Mice
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Mice, SCID
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neoplasm Transplantation
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Oncogene Proteins, Fusion / analysis
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Prognosis
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / physiology
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Remission Induction
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Risk Factors
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Survival Analysis
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Treatment Outcome
Substances
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Biomarkers, Tumor
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins c-bcl-2