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Author  |
Cobaleda, C.; Gutierrez-Cianca, N.; Perez-Losada, J.; Flores, T.; Garcia-Sanz, R.; Gonzalez, M.; Sanchez-Garcia, I. |
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Title |
A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia |
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Journal Article |
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Year |
2000 |
Publication |
Blood |
Abbreviated Journal |
Blood |
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Volume |
95 |
Issue |
3 |
Pages |
1007-1013 |
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Keywords |
ADP-ribosyl Cyclase; Animals; Antigens, CD/analysis; Antigens, CD34/analysis; Antigens, CD38; Antigens, Differentiation/analysis; Antigens, Neoplasm/analysis; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic/*pathology; Fusion Proteins, bcr-abl/physiology; Hematopoietic Stem Cells/classification/*pathology; Humans; Immunophenotyping; Membrane Glycoproteins; Mice; Mice, Inbred NOD; Mice, SCID; NAD+ Nucleosidase/analysis; Neoplasm Transplantation; Neoplastic Stem Cells/classification/*pathology/transplantation; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*pathology |
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Abstract |
BCR-ABL is a chimeric oncogene generated by translocation of sequences from the chromosomal counterpart (c-ABL gene) on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, BCR-ABL(p190) and BCR-ABL(p210), are produced that are characteristic of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(1)-ALL). In CML, the transformation occurs at the level of pluripotent stem cells. However, Ph(1)-ALL is thought to affect progenitor cells with lymphoid differentiation. Here we demonstrate that the cell capable of initiating human Ph(1)-ALL in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID), termed SCID leukemia-initiating cell (SL-IC), possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all Ph(1)-ALL analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34(+ )CD38(-), which is similar to the cell-surface phenotype of normal SCID-repopulating cells. This indicates that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation in Ph(1)-ALL. |
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Address |
Departamento de Proliferacion y Diferenciacion Celular, Instituto de Microbiologia Bioquimica, Universidad de Salamanca, Salamanca, Spain |
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Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Series Volume |
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Edition |
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ISSN |
0006-4971 |
ISBN |
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Area |
WP6 In vivo |
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Conference |
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Notes |
PMID:10648416 |
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no |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
34 |
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