Lack of the adhesion molecules P-selectin and intercellular adhesion molecule-1 accelerate the development of BCR/ABL-induced chronic myeloid leukemia-like myeloproliferative disease in mice
| Autor: | Shawn D. Pelletier, Shaoguang Li, Daniel S. Hong, Yiguo Hu, Yuhua Liu |
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| Rok vydání: | 2004 |
| Předmět: |
DNA
Complementary Time Factors Immunology Intercellular Adhesion Molecule-1 Genetic Vectors Green Fluorescent Proteins Fusion Proteins bcr-abl Bone Marrow Cells Cell Separation Biology Biochemistry Mice hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive medicine Cell Adhesion Animals Cell adhesion Lung ABL Myeloproliferative Disorders Cell adhesion molecule Stem Cells Homozygote breakpoint cluster region Myeloid leukemia Cell Biology Hematology medicine.disease Flow Cytometry Mice Mutant Strains Mice Inbred C57BL Leukemia Luminescent Proteins P-Selectin Retroviridae Mutation Cancer research K562 cells |
| Zdroj: | Blood. 104(7) |
| ISSN: | 0006-4971 |
| Popis: | In vitro studies show that BCR/ABL-expressing hematopoietic cells exhibit altered adhesion properties. No in vivo studies show whether the altered adhesion properties affect BCR/ABL leukemo-genesis. Using mice with homozygous inactivation of genes encoding the 2 adhesion molecules P-selectin and intercellular adhesion molecule-1 (ICAM1), we show that the mutant mice develop BCR/ABL-induced chronic myeloid leukemia (CML)-like leukemia at a significantly faster rate than do wild-type (WT) mice. Lack of P-selectin and ICAM1 did not have a significant effect on the development of B-cell acute lymphoblastic leukemia (BALL) induced by BCR/ABL. Using mice deficient for P-selectin or ICAM1 alone, we show that P-selectin plays a major role in the acceleration of CML-like leukemia. Lack of P-selectin resulted in early release of BCR/ABL-expressing myeloid progenitors from bone marrow, appearing to alter the biologic properties of leukemic cells rather than their growth rate by increasing their homing to the lungs, causing fatal lung hemorrhages. These results indicate that adhesion of BCR/ABL-expressing myeloid progenitors to marrow stroma through P-selectin and ICAM1 play an inhibitory role in the development of CML-like disease, suggesting that improvement of adhesion between BCR/ABL-expressing myeloid progenitor cells and bone marrow stroma may be of therapeutic value for human CML. (Blood. 2004;104:2163-2171) |
| Databáze: | OpenAIRE |
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