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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1997-10-23
pubmed:abstractText
In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1605-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9324277-Acute Disease, pubmed-meshheading:9324277-Adult, pubmed-meshheading:9324277-Amino Acid Sequence, pubmed-meshheading:9324277-Base Sequence, pubmed-meshheading:9324277-DNA, Neoplasm, pubmed-meshheading:9324277-Hematologic Neoplasms, pubmed-meshheading:9324277-Humans, pubmed-meshheading:9324277-Leukemia, Myeloid, pubmed-meshheading:9324277-Molecular Sequence Data, pubmed-meshheading:9324277-Mutation, pubmed-meshheading:9324277-Myelodysplastic Syndromes, pubmed-meshheading:9324277-Protein Structure, Tertiary, pubmed-meshheading:9324277-Proto-Oncogene Proteins, pubmed-meshheading:9324277-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:9324277-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:9324277-Tumor Cells, Cultured, pubmed-meshheading:9324277-fms-Like Tyrosine Kinase 3
pubmed:year
1997
pubmed:articleTitle
Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines.
pubmed:affiliation
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't