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rdf:type |
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lifeskim:mentions |
umls-concept:C0012634,
umls-concept:C0026809,
umls-concept:C0044602,
umls-concept:C0205191,
umls-concept:C0205263,
umls-concept:C0439677,
umls-concept:C0598766,
umls-concept:C1334043,
umls-concept:C1514562,
umls-concept:C1514873,
umls-concept:C1518071,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1879547,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C2697616
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pubmed:issue |
1
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pubmed:dateCreated |
2001-1-22
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pubmed:abstractText |
The effect of mutations in the Src homology 2 (SH2) domain of the BCR/ABL oncogene on leukemogenesis was tested in a quantitative murine bone marrow transduction/transplantation assay that accurately models human Philadelphia-positive B-lymphoid leukemia and chronic myeloid leukemia (CML). The SH2 domain was not required for induction of B-lymphoid leukemia in mice by BCR/ABL. Under conditions where the p190 and p210 forms of BCR/ABL induce fatal CML-like myeloproliferative disease within 4 weeks, p210 SH2 mutants induced CML-like disease in some mice only after a significant delay, with other recipients succumbing to B-lymphoid leukemia instead. In contrast, p190 BCR/ABL SH2 point and deletion mutants rapidly induced CML-like disease. These results provide the first direct evidence of significant differences in cell signaling by the Bcr/Abl tyrosine kinase between these distinct leukemias. Contrary to previous observations, high levels of phosphatidylinositol 3-kinase (PI 3-kinase) activity in primary malignant lymphoblasts and myeloid cells from recipients of marrow transduced with the BCR/ABL SH2 mutants were found. Hence, the decreased induction of CML-like disease by the p210 BCR/ABL SH2 mutants is not due to impaired activation of PI 3-kinase.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4-13
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11133737-Animals,
pubmed-meshheading:11133737-Bone Marrow Cells,
pubmed-meshheading:11133737-Cell Line,
pubmed-meshheading:11133737-Cell Transformation, Neoplastic,
pubmed-meshheading:11133737-Disease Models, Animal,
pubmed-meshheading:11133737-Enzyme Activation,
pubmed-meshheading:11133737-Female,
pubmed-meshheading:11133737-Fusion Proteins, bcr-abl,
pubmed-meshheading:11133737-Interleukin-3,
pubmed-meshheading:11133737-Leukemia, B-Cell,
pubmed-meshheading:11133737-Leukemia, Experimental,
pubmed-meshheading:11133737-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:11133737-Male,
pubmed-meshheading:11133737-Mice,
pubmed-meshheading:11133737-Mice, Inbred BALB C,
pubmed-meshheading:11133737-Myeloid Cells,
pubmed-meshheading:11133737-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11133737-Phosphorylation,
pubmed-meshheading:11133737-Phosphotyrosine,
pubmed-meshheading:11133737-Point Mutation,
pubmed-meshheading:11133737-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:11133737-Protein Binding,
pubmed-meshheading:11133737-Signal Transduction,
pubmed-meshheading:11133737-Stem Cells,
pubmed-meshheading:11133737-src Homology Domains
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pubmed:year |
2001
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pubmed:articleTitle |
The src homology 2 domain of Bcr/Abl is required for efficient induction of chronic myeloid leukemia-like disease in mice but not for lymphoid leukemogenesis or activation of phosphatidylinositol 3-kinase.
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pubmed:affiliation |
Center for Blood Research, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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