Resistance of t(4;11) (MLL-AF4 fusion gene) leukemias to stress-induced cell death: possible mechanism for extensive extramedullary accumulation of cells and poor prognosis
Autor: | M Oberto, John H. Kersey, D Wang |
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Rok vydání: | 1998 |
Předmět: |
Cancer Research
Programmed cell death Cell Survival Cellular homeostasis Biology Translocation Genetic Fusion gene hemic and lymphatic diseases Acute lymphocytic leukemia Proto-Oncogenes Tumor Cells Cultured medicine Humans Child Chromosomes Human Pair 11 Cell Cycle Nuclear Proteins Zinc Fingers Histone-Lysine N-Methyltransferase Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Cell cycle Prognosis medicine.disease Burkitt Lymphoma Artificial Gene Fusion DNA-Binding Proteins Kinetics Leukemia medicine.anatomical_structure Oncology Apoptosis Immunology Bone marrow Chromosomes Human Pair 4 Transcriptional Elongation Factors Cell Division Myeloid-Lymphoid Leukemia Protein Transcription Factors |
Zdroj: | Leukemia. 12:1561-1564 |
ISSN: | 1476-5551 0887-6924 |
Popis: | Acute leukemias of the t(4;11) (MLL-AF4 fusion gene) type frequently have high white blood counts and extramedullary disease in multiple organs. In the present study we evaluated the hypotheses that this extensive disease is the result of extramedullary survival of leukemia cells due to resistance to stress-induced cell death. Leukemias with t(4;11)(MLL-AF4) were found to be resistant to the cell death that results from serum deprivation in vitro when compared with B lineage acute leukemias without t(4;11)(MLL-AF4). Cells with t(4;11)(MLL-AF4) did not have increased doubling time or increased numbers of cells in cycle. These results suggest that the alteration in cellular homeostasis in these leukemias is due to abnormalities of cellular destruction rather than cellular proliferation when compared to other leukemias. Our results are consistent with the hypothesis that death of non-t(4;11) leukemias occurs in the microenvironment outside of the bone marrow as a result of deficient cellular and humoral growth factors. Resistance to death signals in t(4;11) leukemias results in extensive accumulation of leukemia cells in extramedullary sites and likely contributes to the poor prognosis of these leukemias. |
Databáze: | OpenAIRE |
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