Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12).
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.
Kuno
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. kunoy@tsuru.med.nagoya-u.ac.jp
Abe
A
A
Emi
N
N
Iida
M
M
Yokozawa
T
T
Towatari
M
M
Tanimoto
M
M
Saito
H
H
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002522:Chlorocebus aethiops; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics* / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics* / Q000648:ultrastructure; D019281:Dimerization; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000502:physiology*; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells / Q000201:enzymology; D018257:Helix-Loop-Helix Motifs; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000201:enzymology / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D000072377:Syk Kinase; D014162:Transfection; D014178:Translocation, Genetic; D018909:src Homology Domains
D004792:Enzyme Precursors; D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; C000588904:TEL-Syk fusion protein, human; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse