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1. Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy

Author

Frank, Daria, Patnana, Pradeep Kumar, Vorwerk, Jan, Mao, Lianghao, Gopal, Lavanya Mokada, Jung, Noelle, Hennig, Thorben, Ruhnke, Leo, Frenz, Joris Maximillian, Kuppusamy, Maithreyan, Autry, Robert, Wei, Lanying, Sun, Kaiyan, Mohammed Ahmed, Helal Mohammed, Künstner, Axel, Busch, Hauke, Müller, Heiko, Hutter, Stephan, Hoermann, Gregor, Liu, Longlong, Xie, Xiaoqing, Al-Matary, Yahya, Nimmagadda, Subbaiah Chary, Cano, Fiorella Charles, Heuser, Michael, Thol, Felicitas, Göhring, Gudrun, Steinemann, Doris, Thomale, Jürgen, Leitner, Theo, Fischer, Anja, Rad, Roland, Röllig, Christoph, Altmann, Heidi, Kunadt, Desiree, Berdel, Wolfgang E., Hüve, Jana, Neumann, Felix, Klingauf, Jürgen, Calderon, Virginie, Opalka, Bertram, Dührsen, Ulrich, Rosenbauer, Frank, Dugas, Martin, Varghese, Julian, Reinhardt, Hans Christian, von Bubnoff, Nikolas, Möröy, Tarik, Lenz, Georg, Batcha, Aarif M. N., Giorgi, Marianna, Selvam, Murugan, Wang, Eunice, McWeeney, Shannon K., Tyner, Jeffrey W., Stölzel, Friedrich, Mann, Matthias, Jayavelu, Ashok Kumar, and Khandanpour, Cyrus

Published
2023
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3. AML Associated Mesenchymal Stroma Cells Support Growth of AML Cells As a Result of Activated Notch Signaling and This Can be Targeted By Dexamethasone

Author

Ahmed, Helal Mohammed Mohammed Ahmed, primary, Al-Matary, Yahya Saleh, additional, Nimmagadda, Subbaiah Chary, additional, Fiori, Maren, additional, Patnana, Pradeep Kumar, additional, Frank, Daria, additional, Wei, Lanying, additional, Schütte, Judith, additional, May, Tobias, additional, Goethert, Joachim R., additional, Schroeder, Thomas, additional, Buttkereit, Ulrike, additional, Recher, Christian, additional, Rodríguez-Paredes, Manuel, additional, Koenig, Thorsten, additional, Hartmann, Wolfgang, additional, Tuckermann, Jan, additional, Opalka, Bertram, additional, Lenz, Georg, additional, and Khandanpour, Cyrus, additional

Published
2020
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5. the Role of MSCs in the Development of Acute Myeloid Leukemia

Author

Al-Matary, Yahya Saleh, primary, Botezatu, Lacramioara, additional, Fernando Lams, Robert, additional, Thivakaran, Aniththa, additional, Köster, Renata, additional, Schütte, Judith, additional, Dührsen, Ulrich, additional, Opalka, Bertram, additional, and Khandanpour, Cyrus, additional

Published
2016
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7. GFI1b As a Novel Oncosuppressor in AML

Author

Thivakaran, Aniththa, primary, Botezatu, Lacramioara, additional, Hoenes, Judith Maria, additional, Al-Matary, Yahya Saleh, additional, Olberding, Nadine, additional, Schütte, Judith, additional, Köster, Renata, additional, Opalka, Bertram, additional, Dührsen, Ulrich, additional, and Khandanpour, Cyrus, additional

Published
2016
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10. Gfi1 As a Novel Prognostic Marker and Tumor Suppressor In Acute Myeloid Leukemia

Author

Hönes, Judith, primary, Botezatu, Lacramioara, additional, Zeller, Amos, additional, Michel, Lars C., additional, Thiede, Christian, additional, Köster, Renata, additional, Görgens, Andre, additional, van der Reijden, Bert A., additional, Opalka, Bertram, additional, Lennartz, Klaus, additional, Valk, Peter J. M., additional, Giebel, Bernd, additional, Fischer, Karen, additional, Adiprasito, Basri, additional, Heuser, Michael, additional, Löwenberg, Bob, additional, Jansen, Joop H., additional, Ehninger, Gerhard, additional, Dührsen, Ulrich, additional, and Khandanpour, Cyrus, additional

Published
2013
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12. Gfi1b-A Novel Tumor Suppressor In Acute Myeloid Leukemia

Author

Botezatu, Lacramioara, primary, Hönes, Judith, additional, Zeller, Amos, additional, Michel, Lars C., additional, Görgens, Andre, additional, Lennartz, Klaus, additional, Köster, Renata, additional, Opalka, Bertram, additional, Giebel, Bernd, additional, Dührsen, Ulrich, additional, and Khandanpour, Cyrus, additional

Published
2013
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17. Therapy-Associated Immunosuppression and Opportunistic Infections in Multiple Myeloma Patients.

Author

Schutt, Philipp, primary, Brandhorst, Dieter, additional, Stellberg, Werner, additional, Poser, Miriam, additional, Ebeling, Peter, additional, Muller, Siemke, additional, Buttkereit, Ulrike, additional, Opalka, Bertram, additional, Lindemann, Monika, additional, Grosse-Wilde, Hans, additional, Seeber, Siegfried, additional, Moritz, Thomas, additional, and Nowrousian, Mohammad R., additional

Published
2005
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19. Germline variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy

Author

Frank, Daria, Patnana, Pradeep Kumar, Vorwerk, Jan, Mao, Lianghao, Gopal, Lavanya Mokada, Jung, Noelle, Henning, Thorben, Ruhnke, Leo, Frenz, Joris Maximillian, Kuppusamy, Maithreyan, Autry, Robert, Wei, Lanying, Sun, Kaiyan, Mohammed Ahmed, Helal Mohammed, Künstner, Axel, Busch, Hauke, Müller, Heiko, Hutter, Stephan, Hoermann, Gregor, Liu, Longlong, Xie, Xiaoqing, Al-Matary, Yahya, Nimmagadda, Subbaiah Chary, Charles Cano, Fiorella, Heuser, Michael, Thol, Felicitas, Göhring, Gudrun, Steinemann, Doris, Thomale, Jürgen, Leitner, Theo, Fischer, Anja, Rad, Roland, Röllig, Christoph, Altmann, Heidi, Kunadt, Desiree, Berdel, Wolfgang E., Hüve, Jana, Neumann, Felix, Klingauf, Jürgen, Calderon, Virginie, Opalka, Bertram, Dührsen, Ulrich, Rosenbauer, Frank, Dugas, Martin, Varghese, Julian, Reinhardt, Hans Christian, von Bubnoff, Nikolas, Möröy, Tarik, Lenz, Georg, Batcha, Aarif M. N., Giorgi, Marianna, Selvam, Murugan, Wang, Eunice, McWeeney, Shannon K., Tyner, Jeffrey W., Stölzel, Friedrich, Mann, Matthias, Jayavelu, Ashok Kumar, and Khandanpour, Cyrus

Abstract

-Presence of GFI1-36N impedes homologous recombination and MGMT-mediated DNA repair selectively in AML cells.-Use of temozolomide and olaparib allows selective targeting of GFI1-36Nleukemic cells.

Published
2023
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21. Minimal Residual Disease in Patients With Chronic Myelogenous Leukemia Undergoing Long-term Treatment With Recombinant Interferon a-2b Alone or in Combination With Interferon γ

Author

Opalka, Bertram, Wandl, Ursula Brigitte, Becher, Reinhard, Kloke, Otto, Nagel-Hiemke, Marianne, Moritz, Thomas, Beer, Ulrike, Seeber, Siegfried, and Niederle, Norbert

Abstract

Interferon (IFN) therapy has become widely used for the treatment of chronic myelogenous leukemia. Hematologic remissions can be induced in about 60% of patients. Moreover, in a small number of patients loss of the Philadelphia (Ph) chromosome and of the BCR-ABL rearrangement is observed. We have used genomic Southern blotting as well as a two-step polymerase chain reaction (PCR) method to score for BCR-ABL messenger RNA (mRNA) in patients with hematologic remission induced by treatment with IFNα-2b alone or in combination with IFNγ. Concomitantly, cytogenetic analysis was performed. In 11 of 115 patients reported here, a complete loss of rearranged BCR fragments was observed in Southern blots of peripheral blood (PB) and/or bone marrow (BM) cell samples. Malignant marker bands disappeared first in the PB. In six patients, this genotype remained stable, whereas in five patients, low-intensity, rearranged bands reappeared despite continuation of treatment. The reappearance of the malignant marker was not accompanied by a clinical relapse. Ph-negative metaphases were observed in PB cells of four patients and in the PB and BM cells of two of these patients. In the samples of the other patients, residual Ph-positive cells were detected. By two-step PCR, residual BCR-ABL rearranged transcripts were found in samples of 10 patients.

Published
1991
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22. Prolonged Administration of Interferon-α in Patients With Chronic-Phase Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia Before Allogeneic Bone Marrow Transplantation May Adversely Affect Transplant Outcome

Author

Beelen, Dietrich W., Graeven, Ullrich, Elmaagacli, Ahmet H., Niederle, Norbert, Kloke, Otto, Opalka, Bertram, and Schaefer, Ulrich W.

Abstract

To assess the influence of pretransplant cytoreductive therapy with special reference to interferon-α (IFN-α) treatment on major endpoints of allogeneic bone marrow transplantation (BMT), we studied 133 consecutive patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in first chronic phase who received marrow grafts from HLA-identical family (n = 103) or alternative donors (n = 30) at a referral-based transplant center. Fifty of these patients (38%) were previously exposed to IFN-α for a median duration of 14 months (range, 1 to 61 months), whereas 83 patients (62%) exclusively received hydroxyurea and/or busulfan therapy between 1 and 129 months (median, 15 months) pretransplant. Using the categorized treatment duration with each pretransplant cytoreductive agent as a measure for individual patient exposure to each agent, prolonged (>12 months) IFN-α administration was identified as the sole significant pretransplant therapy-related predictor of transplant outcome by proportional hazards regression analysis. The adjusted risk ratio (RR) of transplant-related mortality (TRM) was 2.5-fold higher (95% confidence limits [95% CL], 1.4 to 4.5; P< .004) compared with other pretransplant therapy and this was mainly attributable to a 3.1-fold higher RR (95% CL, 1.4 to 6.4; P< .005) of fatal posttransplant infections after prolonged IFN-α treatment pretransplant. Marrow graft failure developed exclusively among 7 of 30 patients (23%) with donors other than HLA-identical family members and was further restricted to patients who had been previously exposed to IFN-α. The probability of graft failure was 49% ± 28% in 17 patients pretreated with IFN-α compared with 0% for the other 13 patients with mismatched family or unrelated donors (P< .008). In addition, a significant delay in neutrophil and platelet count re-constitution was observed among patients with donors other than HLA-identical family members after pretransplant IFN-α exposure. No influence of pretransplant cytoreductive therapy on either acute and chronic graft-versus-host disease or leukemic relapse was detected in this study. As a consequence of its adverse effect on TRM, prolonged pretransplant IFN-α treatment was independently associated with a 2.5-fold lower likelihood (95% CL, 1.4 to 4.5; P < .003) of 5-year overall survival and with a 2.3-fold lower likelihood (95% CL, 1.3 to 4.2; P < .004) of 5-year disease-free survival postransplant after adjustment for other significant prognostic factors in multivariate analysis. In conclusion, the present study strongly suggests that prolonged pretransplant IFN-α administration in patients with chronic-phase Ph1-positive CML may be associated with an increased risk of fatal transplant-related complications and an inferior outcome after allogeneic BMT. Future analyses on transplant results in chronic-phase CML patients should carefully evaluate the impact of treatment duration or, if applicable, of the cumulative doses of IFN-α and other cytoreductive agents administered pretransplant.

Published
1995
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23. A PvuII Polymorphism of the bcr Region in Patients With Hematopoietic Disorders and Their Families

Author

Opalka, Bertram, Wandl, Ursula, Kloke, Otto, Oberle, Claudia, Koppe, Jutta, Niederle, Norbert, and Schmidt, Carl Gottfried

Abstract

The BCR gene on chromosome 22 has received increasing attention because of its involvement in the Philadelphia (Ph' ') translocation. For most restriction enzymes, this locus has been found to be nonpolymorphic. Two alleles have only been found when Taql-digested DNA is hybridized to a 5’ bcr-specific probe. We describe another two-allele polymorphism detected by the same probe in Pvull-digested DNA. The polymorphism is characterized by an additional PvuII site in the bcr region: this causes the appearance of an additional band of about 2.3 kb or 2.5 kb besides a 4.8-kb fragment in hybridizations with the 5’ bcr or a 3’ bcr probe. The incidence of the second allele is very low. It has only been found in some patients with hematopoietic malignancies and in a group of volunteers having a leukemia patient in their families.

Published
1989
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24. Deletion Of The Von Hippel-LindauGene Interferes With The Development Of Peripheral B-Cell Subsets

Author

Händschke, Kathrin, Weber, Stefanie, Necke, Mandy, Hollenbeck, Anita, Opalka, Bertram, Dührsen, Ulrich, and Göthert, Joachim Rudolf

Abstract

The development of hematopoietic cells occurs in highly specialized microenvironments within bone marrow, thymus and spleen. Hematopoietic stem and progenitor cells are positioned at the lowest end of a bone marrow oxygen gradient, which implies a role for the hypoxic-response pathway in regulating hematopoiesis. In this pathway the von Hippel-Lindau protein (pVhl) is the central negative regulator and continuously mediates the proteasomal destruction of the hypoxia-inducible factor-1α (Hif-1α). Under hypoxic conditions Hif-1α destruction is inhibited and results in the expression of hypoxia-inducible genes.

Published
2013
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25. Gene Transfer of Cytidine Deaminase (CDD) Protects from Cytidine Analogs in an In VivoMurine Transplant Model.

Author

Rattmann, Ina, Sorg, Ursula R., Brueckner, Annette, Opalka, Bertram, Flasshove, Michael, and Moritz, Thomas

Abstract

In vitrogene transfer of CDD protects murine and human hematopoietic cells from cytarabine (araC) and gemcitabine induced toxicity. Thus CDD represents a drug resistance gene with considerable clinical potential. We now have examined CDD gene transfer in a bone marrow transplant model with C57Bl/6 mice using the retroviral vectors SF91-CDD-IRES-EGFP and SFβ1-EGFP (control).

Published
2005
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26. CORRESPONDENCE

Author

OPALKA, BERTRAM, WANDL, URSULA B., STUTENKEMPER, RUTH, KLOKE, OTTO, SEEBER, SIEGFRIED, and NIEDERLE, NORBERT

Published
1992
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