Expression of DNA-PKcs and Ku86, but not Ku70, differs between lymphoid malignancies.
We have investigated the role of DNA-dependent protein kinase (DNA-PK) and related it to proliferation and maturation of different lymphoid malignancies. DNA-PK and Ki-67 protein content was investigated in tumour samples of lymphoid malignancies, obtained from patients with low- and high-grade lymphomas, acute lymphoblastic leukaemia and multiple myeloma. All patients were untreated before sampling. Normal bone marrow, reactive tonsillar tissue and ordinary lymph node tissue were used as controls. We show here that lymphoid malignancies display differences in DNA-PK protein expression. Low-grade lymphoma, appearing as chronic lymphocytic leukaemia (CLL) displayed a significantly lower frequency of cells staining positive for DNA-PKcs and Ku86, but surprisingly not for Ku70, compared with acute lymphoblastic leukaemia (ALL) cells. When material from individual CLL patients was investigated, cells from lymph nodes showed a higher frequency of positive cells with respect to all DNA-PK subunits, compared with CLL cells infiltrating the bone marrow. High-grade lymphoma lymph node samples showed an increased frequency of cells staining positive for DNA-PKcs, Ku86 and Ki-67 compared with lymph node samples from low-grade lymphoma patients. Again, no difference in the Ku70 levels between the two lymphoma entities was noted. In multiple myeloma, the frequency of cells with positive staining for DNA-PKcs was similar to that detected in ALL and high-grade lymphoma. We conclude that with the exception of multiple myeloma, expression of DNA-PK coincides with the degree of maturation of lymphoid malignancies. In low- and high-grade lymphoma, DNA-PK is associated with the proliferation rate.
Holgersson
Asa
A
Unit of Medical Radiation Biology, Karolinska Institutet, CCK, Stockholm, Sweden.
Erdal
Hamdiye
H
Nilsson
Anders
A
Lewensohn
Rolf
R
Kanter
Lena
L
D034961:Antigens, Nuclear / Q000378:metabolism*; D002452:Cell Count; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D015151:Immunoblotting; D019394:Ki-67 Antigen / Q000378:metabolism; D000072200:Ku Autoantigen; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000473:pathology; D008198:Lymph Nodes / Q000201:enzymology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000201:enzymology* / Q000473:pathology; D009101:Multiple Myeloma / Q000201:enzymology / Q000473:pathology; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen