Genotypes and phenotypes of malignant B-cells.

1. Research group name/project:
Genotypes and phenotypes of malignant B-cells.

2. Group leader and some key members (incl. from other depts./inst.):
Trond Stokke (senior scientist), Eivind Galteland (PhD student), Kirsti Solberg Landsverk (PhD student), Marwa Jalal (student), Anne Hansen Ree (collaborator at Dept. of Tumor Biology, DNR).

3. Home address on the internet:
http://radium.no/stokke

4. Department/Institute:
Department of Biophysics.

4b. Hospital (HF):
Det norske radiumhospital HF

5. Main aim of research group:
To study genotypes and phenotypes in primary samples and cell lines from B-cell Non-Hodgkin's lymphoma, with particular focus on the response to ionizing radiation. We are studying cell cycle arrest, apoptosis, and gene expression after irradiation. These "radiation phenotypes" will be correlated to genotypes. The expression of specific genes will be manipulated by the use of e.g. siRNA.

6. Some important recent results (with a few key references):
We have earlier studied genotypes and phenotypes of primary B-cell Non-Hodgkin's lymphomas (Leukemia, 16:1549-1555, 2002, Br J Cancer, 85:1900-1913, 2001, Int J Cancer, 89:313-324, 2000, Br J Cancer, 77:1832-1841, 1998). The focus is now shifted to the effects of ionizing radiation on malignant B-lymphocytes. We have recently discovered that X-irradiation prevents apoptosis induced by mitotic inhibitors in B-cell lines with aberrations in the p53 pathway (Landsverk et al., Rad Res, in press), the reason being that the cells arrest in G2 and are thereby prevented from entering mitosis. Cells with defects in the p53 pathway do not become apoptotic after irradiation alone, and do not arrest in the G1 phase of the cell cycle, in contrast to what is the case for cells with intact p53 function. This is also reflected in the gene expression of these cells after radiation, which has been measured by expression arrays (Stokke et al., manuscript in preparation). We are currently using siRNA against TP53, to more specifically address the role of this gene in the radiation response.

7. Methods in current use:
Microarray (expression and genomic), flow cytometry, fluorescent in situ hybridization, comparative genomic hybridization, transfection of siRNAs and other constructs, PCR.

8. Available equipment:
Flow cytometers, fluorescence microscopes, PCR machines.

9. Collaborators:
9.1. Among Helse Sør hospitals : Paula DeAngelis (RH), Ole Petter F. Clausen (RH).
9.2. Other Norwegian collaborators:
9.3. Collaborators from other countries: David Mu, Tularik Inc., NY, USA.

10. Is the group interested in joining a larger collaborative project in Helse Sør:

11. Tentative name of possible collaborative project(s):

12. Some key search words:
B-cell Non-Hodgkin's lymphoma, genetic aberrations, molecular and cellular phenotypes, ionizing radiation.