TY  - JOUR
AU  - Marinković, Dragan
AU  - Marinković, Tatjana
AU  - Mahr, B
AU  - Hess, J
AU  - Wirth, Thomas
PY  - 2004
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/35
AB  - It is well documented that deregulation of MYC leads to tumor development, yet many aspects of this process are only partially understood. We have established a transgenic mouse model in which c-MYC is conditionally expressed in lymphoid cells using the tetracycline-regulated system of gene regulation. Mice with continuously expressed transgenic c-MYC died of invasive T- or B-cell lymphomas within 4 months. Lymphomas developing in transgenic mice were c-MYC dependent since doxycycline treatment led to tumor regression. Using transplantation of established tumor cell lines labeled with GFP, we followed the fate of neoplastic cells in recipients upon MYC inactivation. This approach allowed us to elucidate both apoptosis and differentiation as mechanisms of tumor elimination. Comparative genomic hybridization (CGH) and FISH analyses were performed in order to analyze possible chromosomal aberrations induced by c-MYC. We observed that overexpression of c-MYC is sufficient to induce recurrent patterns of genomic instability. The main observation was a gain of genomic material that corresponded to chromosome 15 in several T-cell tumors, which could be identified as trisomy.
PB  - Wiley, Hoboken
T2  - International Journal of Cancer
T1  - Reversible lymphomagenesis in conditionally c-MYC expressing mice
EP  - 342
IS  - 3
SP  - 336
VL  - 110
DO  - 10.1002/ijc.20099
ER  - 

@article{
author = "Marinković, Dragan and Marinković, Tatjana and Mahr, B and Hess, J and Wirth, Thomas",
year = "2004",
abstract = "It is well documented that deregulation of MYC leads to tumor development, yet many aspects of this process are only partially understood. We have established a transgenic mouse model in which c-MYC is conditionally expressed in lymphoid cells using the tetracycline-regulated system of gene regulation. Mice with continuously expressed transgenic c-MYC died of invasive T- or B-cell lymphomas within 4 months. Lymphomas developing in transgenic mice were c-MYC dependent since doxycycline treatment led to tumor regression. Using transplantation of established tumor cell lines labeled with GFP, we followed the fate of neoplastic cells in recipients upon MYC inactivation. This approach allowed us to elucidate both apoptosis and differentiation as mechanisms of tumor elimination. Comparative genomic hybridization (CGH) and FISH analyses were performed in order to analyze possible chromosomal aberrations induced by c-MYC. We observed that overexpression of c-MYC is sufficient to induce recurrent patterns of genomic instability. The main observation was a gain of genomic material that corresponded to chromosome 15 in several T-cell tumors, which could be identified as trisomy.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Cancer",
title = "Reversible lymphomagenesis in conditionally c-MYC expressing mice",
pages = "342-336",
number = "3",
volume = "110",
doi = "10.1002/ijc.20099"
}

Marinković, D., Marinković, T., Mahr, B., Hess, J.,& Wirth, T.. (2004). Reversible lymphomagenesis in conditionally c-MYC expressing mice. in International Journal of Cancer
Wiley, Hoboken., 110(3), 336-342.
https://doi.org/10.1002/ijc.20099

Marinković D, Marinković T, Mahr B, Hess J, Wirth T. Reversible lymphomagenesis in conditionally c-MYC expressing mice. in International Journal of Cancer. 2004;110(3):336-342.
doi:10.1002/ijc.20099 .

Marinković, Dragan, Marinković, Tatjana, Mahr, B, Hess, J, Wirth, Thomas, "Reversible lymphomagenesis in conditionally c-MYC expressing mice" in International Journal of Cancer, 110, no. 3 (2004):336-342,
https://doi.org/10.1002/ijc.20099 . .

TY  - JOUR
AU  - Samardžić, T.
AU  - Gerlach, J
AU  - Muller, K
AU  - Marinković, Dragan
AU  - Hess, J
AU  - Nitschke, L.
AU  - Wirth, Thomas
PY  - 2002
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/29
AB  - BOB.1/OBF1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1 xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca2+ mobilization. This Ca2+-signalling defect was restored in BOBA/ OBF1 xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - European Journal of Immunology
T1  - CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice
EP  - 2489
IS  - 9
SP  - 2481
VL  - 32
DO  - 10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C
ER  - 

@article{
author = "Samardžić, T. and Gerlach, J and Muller, K and Marinković, Dragan and Hess, J and Nitschke, L. and Wirth, Thomas",
year = "2002",
abstract = "BOB.1/OBF1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1 xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca2+ mobilization. This Ca2+-signalling defect was restored in BOBA/ OBF1 xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "European Journal of Immunology",
title = "CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice",
pages = "2489-2481",
number = "9",
volume = "32",
doi = "10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C"
}

Samardžić, T., Gerlach, J., Muller, K., Marinković, D., Hess, J., Nitschke, L.,& Wirth, T.. (2002). CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice. in European Journal of Immunology
Wiley-V C H Verlag Gmbh, Weinheim., 32(9), 2481-2489.
https://doi.org/10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C

Samardžić T, Gerlach J, Muller K, Marinković D, Hess J, Nitschke L, Wirth T. CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice. in European Journal of Immunology. 2002;32(9):2481-2489.
doi:10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C .

Samardžić, T., Gerlach, J, Muller, K, Marinković, Dragan, Hess, J, Nitschke, L., Wirth, Thomas, "CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice" in European Journal of Immunology, 32, no. 9 (2002):2481-2489,
https://doi.org/10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C . .