|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0021270,
umls-concept:C0023452,
umls-concept:C0026882,
umls-concept:C0332183,
umls-concept:C0332285,
umls-concept:C0919528,
umls-concept:C1305143,
umls-concept:C1333568,
umls-concept:C1511695,
umls-concept:C1519724,
umls-concept:C1879547
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2004-1-19
|
|
pubmed:abstractText |
Point mutations of D835/I836 of the FLT3 gene have been reported in adult acute myeloid leukemia (AML), but not in pediatric AML or acute lymphoblastic leukemia (ALL). FLT3-D835/I836 mutations were found in 6 (5.4%) of 112 children with ALL older than 1 year and in 8 (16.0%) of 50 infants with ALL. Missense mutations were found in 11 patients, 3-base pair deletions in 2 patients, and a deletion/insertion in 1 patient. Remarkably, FLT3-D835/I836 mutations were found in 8 (18.2%) of 44 infants with ALL with MLL rearrangements and in 4 (21.5%) of 19 patients with hyperdiploid ALL, but they were not found in any patients older than 1 year who had TEL-AML1 (n = 11), E2APBX1 (n = 4), or BCR-ABL (n = 6) fusion genes. Although infant ALL patients with mutations had poorer prognoses than did those without mutations, pediatric ALL patients with mutations who were older than 1 year had good prognoses. We also found FLT3-D835 mutations in 2 of 11 leukemic cell lines with MLL rearrangements. FLT3 was highly phosphorylated in these cell lines with FLT3-D835 mutations, leading to constitutive activation of downstream targets such as signal transducer and activator of transcription 5 (STAT5) without FLT3 ligand stimulation. These results suggested that FLT3-D835/I836 mutations are one of the second genetic events in infant ALL with MLL rearrangements or pediatric ALL with hyperdiploidy.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FLT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MLL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid-Lymphoid Leukemia Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/fms-Like Tyrosine Kinase 3
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0006-4971
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
103
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1085-8
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:14504097-Aneuploidy,
pubmed-meshheading:14504097-Cell Line, Tumor,
pubmed-meshheading:14504097-Child,
pubmed-meshheading:14504097-Child, Preschool,
pubmed-meshheading:14504097-DNA-Binding Proteins,
pubmed-meshheading:14504097-Female,
pubmed-meshheading:14504097-Gene Rearrangement,
pubmed-meshheading:14504097-Humans,
pubmed-meshheading:14504097-Infant,
pubmed-meshheading:14504097-Male,
pubmed-meshheading:14504097-Milk Proteins,
pubmed-meshheading:14504097-Mutation,
pubmed-meshheading:14504097-Mutation, Missense,
pubmed-meshheading:14504097-Myeloid-Lymphoid Leukemia Protein,
pubmed-meshheading:14504097-Oncogene Proteins, Fusion,
pubmed-meshheading:14504097-Phosphorylation,
pubmed-meshheading:14504097-Point Mutation,
pubmed-meshheading:14504097-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:14504097-Prognosis,
pubmed-meshheading:14504097-Protein Structure, Tertiary,
pubmed-meshheading:14504097-Proto-Oncogene Proteins,
pubmed-meshheading:14504097-Proto-Oncogenes,
pubmed-meshheading:14504097-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:14504097-STAT5 Transcription Factor,
pubmed-meshheading:14504097-Sequence Deletion,
pubmed-meshheading:14504097-Trans-Activators,
pubmed-meshheading:14504097-Transcription Factors,
pubmed-meshheading:14504097-fms-Like Tyrosine Kinase 3
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy.
|
|
pubmed:affiliation |
Gunma Children's Medical Center, 779 Shimohadoka, Kitatachibana, Gunma 377-8577, Japan. hayashiy-tky@umin.ac.jp
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
