Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas.
Peripheral T-cell lymphomas (PTCLs) are fatal in the majority of patients and novel treatments, such as protein tyrosine kinase (PTK) inhibition, are needed. The recent finding of SYK/ITK translocations in rare PTCLs led us to examine the expression of Syk PTK in 141 PTCLs. Syk was positive by immunohistochemistry (IHC) in 133 PTCLs (94%), whereas normal T cells were negative. Western blot on frozen tissue (n=6) and flow cytometry on cell suspensions (n=4) correlated with IHC results in paraffin. Additionally, western blot demonstrated that Syk-positive PTCLs show tyrosine (525/526) phosphorylation, known to be required for Syk activation. Fluorescence in situ hybridization showed no SYK/ITK translocation in 86 cases. Overexpression of Syk, phosphorylation of its Y525/526 residues and the availability of orally available Syk inhibitors suggest that Syk merits further evaluation as a candidate target for pharmacologic PTK inhibition in patients with PTCL.
Feldman
A L
AL
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. feldman.andrew@mayo.edu
Sun
D X
DX
Law
M E
ME
Novak
A J
AJ
Attygalle
A D
AD
Thorland
E C
EC
Fink
S R
SR
Vrana
J A
JA
Caron
B L
BL
Morice
W G
WG
Remstein
E D
ED
Grogg
K L
KL
Kurtin
P J
PJ
Macon
W R
WR
Dogan
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D054391:Lymphoma, Extranodal NK-T-Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000072377:Syk Kinase; D014178:Translocation, Genetic; D014443:Tyrosine / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C080813:emt protein-tyrosine kinase