Decreased platelet expression of myosin regulatory light chain polypeptide (MYL9) and other genes with platelet dysfunction and CBFA2/RUNX1 mutation: insights from platelet expression profiling
| Autor: | L. Sun, E. P. Hoffman, J. R. Gorospe, AK Rao |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Blood Platelets Male Myosin light-chain kinase Myosin Light Chains GTPase-activating protein Immunoblotting Down-Regulation Biology Calcium-binding protein Cluster Analysis Humans Platelet Platelet activation RNA Messenger Abnormal Platelet Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Impaired platelet aggregation Reproducibility of Results Hematology Platelet Activation Molecular biology Thrombocytopenia Core Binding Factor Alpha 2 Subunit Mutation MYL9 |
| Zdroj: | Journal of thrombosis and haemostasis : JTH. 5(1) |
| ISSN: | 1538-7933 |
| Popis: | We have reported on a patient with thrombocytopenia, impaired platelet aggregation, secretion, phosphorylation of pleckstrin and myosin light chain (MLC), and GPIIb-IIIa activation, associated with a heterozygous mutation in transcription factor CBFA2 (core binding factor A2, RUNX1 or AML1). To obtain insights into the abnormal platelet mechanisms and CBFA2-regulated genes, we performed platelet expression profiling in four control subjects and the patient using the Affymetrix U133 GeneChips. In the patient, 298 probe sets were significantly downregulated at least 2-fold. MLC regulatory polypeptide (MYL9 gene) was decreased approximately 77-fold; this is an important finding because agonist-stimulated MLC phosphorylation is decreased in patient platelets. Genes downregulated > or = 5-fold include those involving calcium binding proteins (CABP5), ion transport (sodium/potassium/Ca exchanger, SLC24A3), cytoskeletal/microtubule proteins (erythrocyte membrane protein band 4.1-like 3, EPB41L3; tropomyosin 1, TPM1; tubulin, alpha 1, TUBA1), signaling proteins (RAB GTPase activating protein 1-like, RABGAP1L; beta3-endonexin, ITGB3 BP) and chemokines (platelet factor 4 variant 1, PF4V1; chemokine CXCL5, CXCL5). These and other downregulated genes are relevant to the patient's platelet defects in function and production. These studies provide the first proof of concept that platelet expression profiling can be applied to obtain insights into the molecular basis of inherited platelet defects. |
| Databáze: | OpenAIRE |
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