Abstract
The TEL gene on 12p12-13 is a target for a number of translocations associated with various hematological malignancies. The fusion of the TEL gene to the Syk gene in a patient with myelodysplastic syndrome (MDS) with t(9;12)(q22;p12) is reported. Southern blot analysis of patient bone marrow cells with TEL and Syk gene probes detected rearranged fragments. Anchored polymerase chain reaction identified the Syk gene, a nonreceptor tyrosine kinase, on 9q22 fused downstream of TEL exon 5. The TEL gene was fused in-frame to Syk and produced a fusion protein that was constitutively phosphorylated in tyrosine with dimerization that was mediated by the helix-loop-helix domain of TEL. A TEL-Syk fusion product transformed the murine hematopoietic cell line BaF3 to interleukin-3 growth factor independence. TEL-Syk is a novel transforming protein and leads to the transformation of hematopoietic cells. These data implicate that the rearranged Syk gene is involved in the pathogenesis of hematopoietic malignancies.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
COS Cells
-
Cell Division / drug effects
-
Cell Line / drug effects
-
Cell Transformation, Neoplastic / genetics
-
Chlorocebus aethiops
-
Chromosomes, Human, Pair 12 / genetics*
-
Chromosomes, Human, Pair 12 / ultrastructure
-
Chromosomes, Human, Pair 9 / genetics*
-
Chromosomes, Human, Pair 9 / ultrastructure
-
Dimerization
-
Enzyme Activation
-
Enzyme Precursors / genetics
-
Enzyme Precursors / physiology*
-
Exons / genetics
-
Gene Expression Regulation, Neoplastic
-
HL-60 Cells / enzymology
-
Helix-Loop-Helix Motifs
-
Hematopoietic Stem Cells / drug effects
-
Hematopoietic Stem Cells / enzymology
-
Hematopoietic Stem Cells / pathology
-
Humans
-
Interleukin-3 / pharmacology
-
Intracellular Signaling Peptides and Proteins
-
Mice
-
Myelodysplastic Syndromes / enzymology
-
Myelodysplastic Syndromes / genetics*
-
Oncogene Proteins, Fusion
-
Phosphorylation
-
Protein Processing, Post-Translational*
-
Protein-Tyrosine Kinases / genetics
-
Protein-Tyrosine Kinases / physiology*
-
Recombinant Fusion Proteins
-
Signal Transduction
-
Syk Kinase
-
Transfection
-
Translocation, Genetic*
-
src Homology Domains
Substances
-
Enzyme Precursors
-
Interleukin-3
-
Intracellular Signaling Peptides and Proteins
-
Oncogene Proteins, Fusion
-
Recombinant Fusion Proteins
-
TEL-Syk fusion protein, human
-
Protein-Tyrosine Kinases
-
SYK protein, human
-
Syk Kinase
-
Syk protein, mouse