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1. Delineating MYC-Mediated Escape Mechanisms from Conventional and T Cell-Redirecting Therapeutic Antibodies.

Author

de Jonge, Anna Vera, Csikós, Tamás, Eken, Merve, Bulthuis, Elianne P., Poddighe, Pino J., Roemer, Margaretha G. M., Chamuleau, Martine E. D., and Mutis, Tuna

Abstract

In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma cell lines, as well as patient-derived primary tumor cells, enhances their susceptibility to NK cell-mediated cytotoxicity induced by conventional antibodies targeting CD20 (rituximab) and CD38 (daratumumab), as well as T cell-mediated cytotoxicity induced by the CD19-targeting bispecific T-cell engager blinatumomab. This was associated with upregulation of the target antigen only for rituximab, suggesting additional escape mechanisms. To investigate these mechanisms, we targeted the MYC gene in OCI-LY18 cells using CRISPR-Cas9 gene-editing technology. CRISPR-Cas9-mediated MYC targeting not only upregulated CD20 but also triggered broader apoptotic pathways, upregulating pro-apoptotic PUMA and downregulating anti-apoptotic proteins BCL-2, XIAP, survivin and MCL-1, thereby rendering tumor cells more prone to apoptosis, a key tumor-lysis mechanism employed by T-cells and NK-cells. Moreover, MYC downregulation boosted T-cell activation and cytokine release in response to blinatumomab, revealing a MYC-mediated T-cell suppression mechanism. In conclusion, MYC overexpressing tumor cells mitigated the efficacy of therapeutic antibodies through several non-overlapping mechanisms. Given the challenges associated with direct MYC inhibition due to toxicity, successful modulation of MYC-mediated immune evasion mechanisms may improve the outcome of immunotherapeutic approaches in B-cell malignancies. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Supplementary Figure 3 from Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab

Author

Krejcik, Jakub, primary, Frerichs, Kris A., primary, Nijhof, Inger S., primary, van Kessel, Berris, primary, van Velzen, Jeroen F., primary, Bloem, Andries C., primary, Broekmans, Marloes E.C., primary, Zweegman, Sonja, primary, van Meerloo, Johan, primary, Musters, René J.P., primary, Poddighe, Pino J., primary, Groen, Richard W.J., primary, Chiu, Christopher, primary, Plesner, Torben, primary, Lokhorst, Henk M., primary, Sasser, A. Kate, primary, Mutis, Tuna, primary, and van de Donk, Niels W.C.J., primary

Published
2023
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4. Supplemental Data from Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab

Author

Krejcik, Jakub, primary, Frerichs, Kris A., primary, Nijhof, Inger S., primary, van Kessel, Berris, primary, van Velzen, Jeroen F., primary, Bloem, Andries C., primary, Broekmans, Marloes E.C., primary, Zweegman, Sonja, primary, van Meerloo, Johan, primary, Musters, René J.P., primary, Poddighe, Pino J., primary, Groen, Richard W.J., primary, Chiu, Christopher, primary, Plesner, Torben, primary, Lokhorst, Henk M., primary, Sasser, A. Kate, primary, Mutis, Tuna, primary, and van de Donk, Niels W.C.J., primary

Published
2023
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9. Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells

Author

Glykofridis, Iris E, primary, Knol, Jaco C, additional, Balk, Jesper A, additional, Westland, Denise, additional, Pham, Thang V, additional, Piersma, Sander R, additional, Lougheed, Sinéad M, additional, Derakhshan, Sepide, additional, Veen, Puck, additional, Rooimans, Martin A, additional, van Mil, Saskia E, additional, Böttger, Franziska, additional, Poddighe, Pino J, additional, van de Beek, Irma, additional, Drost, Jarno, additional, Zwartkruis, Fried JT, additional, de Menezes, Renee X, additional, Meijers-Heijboer, Hanne EJ, additional, Houweling, Arjan C, additional, Jimenez, Connie R, additional, and Wolthuis, Rob MF, additional

Published
2021
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13. Author response: Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells

Author

Glykofridis, Iris E, primary, Knol, Jaco C, additional, Balk, Jesper A, additional, Westland, Denise, additional, Pham, Thang V, additional, Piersma, Sander R, additional, Lougheed, Sinéad M, additional, Derakhshan, Sepide, additional, Veen, Puck, additional, Rooimans, Martin A, additional, van Mil, Saskia E, additional, Böttger, Franziska, additional, Poddighe, Pino J, additional, van de Beek, Irma, additional, Drost, Jarno, additional, Zwartkruis, Fried JT, additional, de Menezes, Renee X, additional, Meijers-Heijboer, Hanne EJ, additional, Houweling, Arjan C, additional, Jimenez, Connie R, additional, and Wolthuis, Rob MF, additional

Published
2020
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18. Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies

Author

Hoogeboom A Jeannette M, van de Graaf Raoul, van de Brug Judith C, Douben Hannie, Dieleman Marianne MJ, van der Veken Lars T, Poddighe Pino J, and de Klein Annelies

Subjects
Genetics, QH426-470
Abstract

Abstract Background Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Results We report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BAC-probes located in the region indicated the presence of 6 signals on the r(18) chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy. Conclusions We report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11.

Published
2010
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19. Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report

Author

Rongen Michel A, Hilkmann José TW, Stoevelaar Gerda HT, van Dooren Marieke F, Simon Marleen EH, de Vree Paula JP, Huijbregts Gido CM, Verkerk Annemieke JMH, and Poddighe Pino J

Subjects
Genetics, QH426-470
Abstract

Abstract Background Complex chromosomal rearrangements (CCR) are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes. Results Multicolour fluorescence in situ hybridization (M-FISH) showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients. Conclusion Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.

Published
2009
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21. CD38 as a therapeutic target for adult acute myeloid leukemia and T-cell acute lymphoblastic leukemia

Author

Naik, Jyoti, primary, Themeli, Maria, additional, de Jong-Korlaar, Regina, additional, Ruiter, Ruud W.J., additional, Poddighe, Pino J, additional, Yuan, Huipin, additional, de Bruijn, Joost D., additional, Ossenkoppele, Gert J., additional, Zweegman, Sonja, additional, Smit, Linda, additional, Mutis, Tuna, additional, Martens, Anton C.M., additional, van de Donk, Niels W.C.J., additional, and Groen, Richard W.J., additional

Published
2018
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23. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Author

Redin, Claire, Brand, Harrison, Collins, Ryan L, Kammin, Tammy, Mitchell, Elyse, Hodge, Jennelle C, Hanscom, Carrie, Pillalamarri, Vamsee, Seabra, Catarina M, Abbott, Mary-Alice, Abdul-Rahman, Omar A, Aberg, Erika, Adley, Rhett, Alcaraz-Estrada, Sofia L, Alkuraya, Fowzan S, An, Yu, Anderson, Mary-Anne, Antolik, Caroline, Anyane-Yeboa, Kwame, Atkin, Joan F, Bartell, Tina, Bernstein, Jonathan A, Beyer, Elizabeth, Blumenthal, Ian, Bongers, Ernie M H F, Brilstra, Eva H, Brown, Chester W, Brüggenwirth, Hennie T, Callewaert, Bert, Chiang, Colby, Corning, Ken, Cox, Helen, Cuppen, Edwin, Currall, Benjamin B, Cushing, Tom, David, Dezso, Deardorff, Matthew A, Dheedene, Annelies, D'Hooghe, Marc, de Vries, Bert B A, Earl, Dawn L, Ferguson, Heather L, Fisher, Heather, FitzPatrick, David R, Gerrol, Pamela, Giachino, Daniela, Glessner, Joseph T, Gliem, Troy, Grady, Margo, Graham, Brett H, Griffis, Cristin, Gripp, Karen W, Gropman, Andrea L, Hanson-Kahn, Andrea, Harris, David J, Hayden, Mark A, Hill, Rosamund, Hochstenbach, Ron, Hoffman, Jodi D, Hopkin, Robert J, Hubshman, Monika W, Innes, A Micheil, Irons, Mira, Irving, Melita, Jacobsen, Jessie C, Janssens, Sandra, Jewett, Tamison, Johnson, John P, Jongmans, Marjolijn C, Kahler, Stephen G, Koolen, David A, Korzelius, Jerome, Kroisel, Peter M, Lacassie, Yves, Lawless, William, Lemyre, Emmanuelle, Leppig, Kathleen, Levin, Alex V, Li, Haibo, Li, Hong, Liao, Eric C, Lim, Cynthia, Lose, Edward J, Lucente, Diane, Macera, Michael J, Manavalan, Poornima, Mandrile, Giorgia, Marcelis, Carlo L, Margolin, Lauren, Mason, Tamara, Masser-Frye, Diane, McClellan, Michael W, Mendoza, Cinthya J Zepeda, Menten, Björn, Middelkamp, Sjors, Mikami, Liya R, Moe, Emily, Mohammed, Shehla, Mononen, Tarja, Mortenson, Megan E, Moya, Graciela, Nieuwint, Aggie W, Ordulu, Zehra, Parkash, Sandhya, Pauker, Susan P, Pereira, Shahrin, Perrin, Danielle, Phelan, Katy, Aguilar, Raul E Piña, Poddighe, Pino J, Pregno, Giulia, Raskin, Salmo, Reis, Linda, Rhead, William, Rita, Debra, Renkens, Ivo, Roelens, Filip, Ruliera, Jayla, Rump, Patrick, Schilit, Samantha L P, Shaheen, Ranad, Sparkes, Rebecca, Spiegel, Erica, Stevens, Blair, Stone, Matthew R, Tagoe, Julia, Thakuria, Joseph V, van Bon, Bregje W, van de Kamp, Jiddeke, van Der Burgt, Ineke, van Essen, Ton, van Ravenswaaij-Arts, Conny M, van Roosmalen, Markus J, Vergult, Sarah, Volker-Touw, Catharina M L, Warburton, Dorothy P, Waterman, Matthew J, Wiley, Susan, Wilson, Anna, Yerena-de Vega, Maria de la Concepcion A, Zori, Roberto T, Levy, Brynn, Brunner, Han G, de Leeuw, Nicole, Kloosterman, Wigard P, Thorland, Erik C, Morton, Cynthia C, Gusella, James F, Talkowski, Michael E, Redin, Claire, Brand, Harrison, Collins, Ryan L, Kammin, Tammy, Mitchell, Elyse, Hodge, Jennelle C, Hanscom, Carrie, Pillalamarri, Vamsee, Seabra, Catarina M, Abbott, Mary-Alice, Abdul-Rahman, Omar A, Aberg, Erika, Adley, Rhett, Alcaraz-Estrada, Sofia L, Alkuraya, Fowzan S, An, Yu, Anderson, Mary-Anne, Antolik, Caroline, Anyane-Yeboa, Kwame, Atkin, Joan F, Bartell, Tina, Bernstein, Jonathan A, Beyer, Elizabeth, Blumenthal, Ian, Bongers, Ernie M H F, Brilstra, Eva H, Brown, Chester W, Brüggenwirth, Hennie T, Callewaert, Bert, Chiang, Colby, Corning, Ken, Cox, Helen, Cuppen, Edwin, Currall, Benjamin B, Cushing, Tom, David, Dezso, Deardorff, Matthew A, Dheedene, Annelies, D'Hooghe, Marc, de Vries, Bert B A, Earl, Dawn L, Ferguson, Heather L, Fisher, Heather, FitzPatrick, David R, Gerrol, Pamela, Giachino, Daniela, Glessner, Joseph T, Gliem, Troy, Grady, Margo, Graham, Brett H, Griffis, Cristin, Gripp, Karen W, Gropman, Andrea L, Hanson-Kahn, Andrea, Harris, David J, Hayden, Mark A, Hill, Rosamund, Hochstenbach, Ron, Hoffman, Jodi D, Hopkin, Robert J, Hubshman, Monika W, Innes, A Micheil, Irons, Mira, Irving, Melita, Jacobsen, Jessie C, Janssens, Sandra, Jewett, Tamison, Johnson, John P, Jongmans, Marjolijn C, Kahler, Stephen G, Koolen, David A, Korzelius, Jerome, Kroisel, Peter M, Lacassie, Yves, Lawless, William, Lemyre, Emmanuelle, Leppig, Kathleen, Levin, Alex V, Li, Haibo, Li, Hong, Liao, Eric C, Lim, Cynthia, Lose, Edward J, Lucente, Diane, Macera, Michael J, Manavalan, Poornima, Mandrile, Giorgia, Marcelis, Carlo L, Margolin, Lauren, Mason, Tamara, Masser-Frye, Diane, McClellan, Michael W, Mendoza, Cinthya J Zepeda, Menten, Björn, Middelkamp, Sjors, Mikami, Liya R, Moe, Emily, Mohammed, Shehla, Mononen, Tarja, Mortenson, Megan E, Moya, Graciela, Nieuwint, Aggie W, Ordulu, Zehra, Parkash, Sandhya, Pauker, Susan P, Pereira, Shahrin, Perrin, Danielle, Phelan, Katy, Aguilar, Raul E Piña, Poddighe, Pino J, Pregno, Giulia, Raskin, Salmo, Reis, Linda, Rhead, William, Rita, Debra, Renkens, Ivo, Roelens, Filip, Ruliera, Jayla, Rump, Patrick, Schilit, Samantha L P, Shaheen, Ranad, Sparkes, Rebecca, Spiegel, Erica, Stevens, Blair, Stone, Matthew R, Tagoe, Julia, Thakuria, Joseph V, van Bon, Bregje W, van de Kamp, Jiddeke, van Der Burgt, Ineke, van Essen, Ton, van Ravenswaaij-Arts, Conny M, van Roosmalen, Markus J, Vergult, Sarah, Volker-Touw, Catharina M L, Warburton, Dorothy P, Waterman, Matthew J, Wiley, Susan, Wilson, Anna, Yerena-de Vega, Maria de la Concepcion A, Zori, Roberto T, Levy, Brynn, Brunner, Han G, de Leeuw, Nicole, Kloosterman, Wigard P, Thorland, Erik C, Morton, Cynthia C, Gusella, James F, and Talkowski, Michael E

Published
2017

24. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Author

Genetica Klinische Genetica, Brain, CMM, Circulatory Health, Cancer, Child Health, Genetica Sectie Genoomdiagnostiek, CMM Groep Cuppen, Genetica, CMM Groep Kloosterman, Redin, Claire, Brand, Harrison, Collins, Ryan L, Kammin, Tammy, Mitchell, Elyse, Hodge, Jennelle C, Hanscom, Carrie, Pillalamarri, Vamsee, Seabra, Catarina M, Abbott, Mary-Alice, Abdul-Rahman, Omar A, Aberg, Erika, Adley, Rhett, Alcaraz-Estrada, Sofia L, Alkuraya, Fowzan S, An, Yu, Anderson, Mary-Anne, Antolik, Caroline, Anyane-Yeboa, Kwame, Atkin, Joan F, Bartell, Tina, Bernstein, Jonathan A, Beyer, Elizabeth, Blumenthal, Ian, Bongers, Ernie M H F, Brilstra, Eva H, Brown, Chester W, Brüggenwirth, Hennie T, Callewaert, Bert, Chiang, Colby, Corning, Ken, Cox, Helen, Cuppen, Edwin, Currall, Benjamin B, Cushing, Tom, David, Dezso, Deardorff, Matthew A, Dheedene, Annelies, D'Hooghe, Marc, de Vries, Bert B A, Earl, Dawn L, Ferguson, Heather L, Fisher, Heather, FitzPatrick, David R, Gerrol, Pamela, Giachino, Daniela, Glessner, Joseph T, Gliem, Troy, Grady, Margo, Graham, Brett H, Griffis, Cristin, Gripp, Karen W, Gropman, Andrea L, Hanson-Kahn, Andrea, Harris, David J, Hayden, Mark A, Hill, Rosamund, Hochstenbach, Ron, Hoffman, Jodi D, Hopkin, Robert J, Hubshman, Monika W, Innes, A Micheil, Irons, Mira, Irving, Melita, Jacobsen, Jessie C, Janssens, Sandra, Jewett, Tamison, Johnson, John P, Jongmans, Marjolijn C, Kahler, Stephen G, Koolen, David A, Korzelius, Jerome, Kroisel, Peter M, Lacassie, Yves, Lawless, William, Lemyre, Emmanuelle, Leppig, Kathleen, Levin, Alex V, Li, Haibo, Li, Hong, Liao, Eric C, Lim, Cynthia, Lose, Edward J, Lucente, Diane, Macera, Michael J, Manavalan, Poornima, Mandrile, Giorgia, Marcelis, Carlo L, Margolin, Lauren, Mason, Tamara, Masser-Frye, Diane, McClellan, Michael W, Mendoza, Cinthya J Zepeda, Menten, Björn, Middelkamp, Sjors, Mikami, Liya R, Moe, Emily, Mohammed, Shehla, Mononen, Tarja, Mortenson, Megan E, Moya, Graciela, Nieuwint, Aggie W, Ordulu, Zehra, Parkash, Sandhya, Pauker, Susan P, Pereira, Shahrin, Perrin, Danielle, Phelan, Katy, Aguilar, Raul E Piña, Poddighe, Pino J, Pregno, Giulia, Raskin, Salmo, Reis, Linda, Rhead, William, Rita, Debra, Renkens, Ivo, Roelens, Filip, Ruliera, Jayla, Rump, Patrick, Schilit, Samantha L P, Shaheen, Ranad, Sparkes, Rebecca, Spiegel, Erica, Stevens, Blair, Stone, Matthew R, Tagoe, Julia, Thakuria, Joseph V, van Bon, Bregje W, van de Kamp, Jiddeke, van Der Burgt, Ineke, van Essen, Ton, van Ravenswaaij-Arts, Conny M, van Roosmalen, Markus J, Vergult, Sarah, Volker-Touw, Catharina M L, Warburton, Dorothy P, Waterman, Matthew J, Wiley, Susan, Wilson, Anna, Yerena-de Vega, Maria de la Concepcion A, Zori, Roberto T, Levy, Brynn, Brunner, Han G, de Leeuw, Nicole, Kloosterman, Wigard P, Thorland, Erik C, Morton, Cynthia C, Gusella, James F, Talkowski, Michael E, Genetica Klinische Genetica, Brain, CMM, Circulatory Health, Cancer, Child Health, Genetica Sectie Genoomdiagnostiek, CMM Groep Cuppen, Genetica, CMM Groep Kloosterman, Redin, Claire, Brand, Harrison, Collins, Ryan L, Kammin, Tammy, Mitchell, Elyse, Hodge, Jennelle C, Hanscom, Carrie, Pillalamarri, Vamsee, Seabra, Catarina M, Abbott, Mary-Alice, Abdul-Rahman, Omar A, Aberg, Erika, Adley, Rhett, Alcaraz-Estrada, Sofia L, Alkuraya, Fowzan S, An, Yu, Anderson, Mary-Anne, Antolik, Caroline, Anyane-Yeboa, Kwame, Atkin, Joan F, Bartell, Tina, Bernstein, Jonathan A, Beyer, Elizabeth, Blumenthal, Ian, Bongers, Ernie M H F, Brilstra, Eva H, Brown, Chester W, Brüggenwirth, Hennie T, Callewaert, Bert, Chiang, Colby, Corning, Ken, Cox, Helen, Cuppen, Edwin, Currall, Benjamin B, Cushing, Tom, David, Dezso, Deardorff, Matthew A, Dheedene, Annelies, D'Hooghe, Marc, de Vries, Bert B A, Earl, Dawn L, Ferguson, Heather L, Fisher, Heather, FitzPatrick, David R, Gerrol, Pamela, Giachino, Daniela, Glessner, Joseph T, Gliem, Troy, Grady, Margo, Graham, Brett H, Griffis, Cristin, Gripp, Karen W, Gropman, Andrea L, Hanson-Kahn, Andrea, Harris, David J, Hayden, Mark A, Hill, Rosamund, Hochstenbach, Ron, Hoffman, Jodi D, Hopkin, Robert J, Hubshman, Monika W, Innes, A Micheil, Irons, Mira, Irving, Melita, Jacobsen, Jessie C, Janssens, Sandra, Jewett, Tamison, Johnson, John P, Jongmans, Marjolijn C, Kahler, Stephen G, Koolen, David A, Korzelius, Jerome, Kroisel, Peter M, Lacassie, Yves, Lawless, William, Lemyre, Emmanuelle, Leppig, Kathleen, Levin, Alex V, Li, Haibo, Li, Hong, Liao, Eric C, Lim, Cynthia, Lose, Edward J, Lucente, Diane, Macera, Michael J, Manavalan, Poornima, Mandrile, Giorgia, Marcelis, Carlo L, Margolin, Lauren, Mason, Tamara, Masser-Frye, Diane, McClellan, Michael W, Mendoza, Cinthya J Zepeda, Menten, Björn, Middelkamp, Sjors, Mikami, Liya R, Moe, Emily, Mohammed, Shehla, Mononen, Tarja, Mortenson, Megan E, Moya, Graciela, Nieuwint, Aggie W, Ordulu, Zehra, Parkash, Sandhya, Pauker, Susan P, Pereira, Shahrin, Perrin, Danielle, Phelan, Katy, Aguilar, Raul E Piña, Poddighe, Pino J, Pregno, Giulia, Raskin, Salmo, Reis, Linda, Rhead, William, Rita, Debra, Renkens, Ivo, Roelens, Filip, Ruliera, Jayla, Rump, Patrick, Schilit, Samantha L P, Shaheen, Ranad, Sparkes, Rebecca, Spiegel, Erica, Stevens, Blair, Stone, Matthew R, Tagoe, Julia, Thakuria, Joseph V, van Bon, Bregje W, van de Kamp, Jiddeke, van Der Burgt, Ineke, van Essen, Ton, van Ravenswaaij-Arts, Conny M, van Roosmalen, Markus J, Vergult, Sarah, Volker-Touw, Catharina M L, Warburton, Dorothy P, Waterman, Matthew J, Wiley, Susan, Wilson, Anna, Yerena-de Vega, Maria de la Concepcion A, Zori, Roberto T, Levy, Brynn, Brunner, Han G, de Leeuw, Nicole, Kloosterman, Wigard P, Thorland, Erik C, Morton, Cynthia C, Gusella, James F, and Talkowski, Michael E

Published
2017

25. Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab

Author

Krejcik, Jakub, primary, Frerichs, Kris A., additional, Nijhof, Inger S., additional, van Kessel, Berris, additional, van Velzen, Jeroen F., additional, Bloem, Andries C., additional, Broekmans, Marloes E.C., additional, Zweegman, Sonja, additional, van Meerloo, Johan, additional, Musters, René J.P., additional, Poddighe, Pino J., additional, Groen, Richard W.J., additional, Chiu, Christopher, additional, Plesner, Torben, additional, Lokhorst, Henk M., additional, Sasser, A. Kate, additional, Mutis, Tuna, additional, and van de Donk, Niels W.C.J., additional

Published
2017
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28. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Author

Redin, Claire, primary, Brand, Harrison, additional, Collins, Ryan L, additional, Kammin, Tammy, additional, Mitchell, Elyse, additional, Hodge, Jennelle C, additional, Hanscom, Carrie, additional, Pillalamarri, Vamsee, additional, Seabra, Catarina M, additional, Abbott, Mary-Alice, additional, Abdul-Rahman, Omar A, additional, Aberg, Erika, additional, Adley, Rhett, additional, Alcaraz-Estrada, Sofia L, additional, Alkuraya, Fowzan S, additional, An, Yu, additional, Anderson, Mary-Anne, additional, Antolik, Caroline, additional, Anyane-Yeboa, Kwame, additional, Atkin, Joan F, additional, Bartell, Tina, additional, Bernstein, Jonathan A, additional, Beyer, Elizabeth, additional, Blumenthal, Ian, additional, Bongers, Ernie M H F, additional, Brilstra, Eva H, additional, Brown, Chester W, additional, Brüggenwirth, Hennie T, additional, Callewaert, Bert, additional, Chiang, Colby, additional, Corning, Ken, additional, Cox, Helen, additional, Cuppen, Edwin, additional, Currall, Benjamin B, additional, Cushing, Tom, additional, David, Dezso, additional, Deardorff, Matthew A, additional, Dheedene, Annelies, additional, D'Hooghe, Marc, additional, de Vries, Bert B A, additional, Earl, Dawn L, additional, Ferguson, Heather L, additional, Fisher, Heather, additional, FitzPatrick, David R, additional, Gerrol, Pamela, additional, Giachino, Daniela, additional, Glessner, Joseph T, additional, Gliem, Troy, additional, Grady, Margo, additional, Graham, Brett H, additional, Griffis, Cristin, additional, Gripp, Karen W, additional, Gropman, Andrea L, additional, Hanson-Kahn, Andrea, additional, Harris, David J, additional, Hayden, Mark A, additional, Hill, Rosamund, additional, Hochstenbach, Ron, additional, Hoffman, Jodi D, additional, Hopkin, Robert J, additional, Hubshman, Monika W, additional, Innes, A Micheil, additional, Irons, Mira, additional, Irving, Melita, additional, Jacobsen, Jessie C, additional, Janssens, Sandra, additional, Jewett, Tamison, additional, Johnson, John P, additional, Jongmans, Marjolijn C, additional, Kahler, Stephen G, additional, Koolen, David A, additional, Korzelius, Jerome, additional, Kroisel, Peter M, additional, Lacassie, Yves, additional, Lawless, William, additional, Lemyre, Emmanuelle, additional, Leppig, Kathleen, additional, Levin, Alex V, additional, Li, Haibo, additional, Li, Hong, additional, Liao, Eric C, additional, Lim, Cynthia, additional, Lose, Edward J, additional, Lucente, Diane, additional, Macera, Michael J, additional, Manavalan, Poornima, additional, Mandrile, Giorgia, additional, Marcelis, Carlo L, additional, Margolin, Lauren, additional, Mason, Tamara, additional, Masser-Frye, Diane, additional, McClellan, Michael W, additional, Mendoza, Cinthya J Zepeda, additional, Menten, Björn, additional, Middelkamp, Sjors, additional, Mikami, Liya R, additional, Moe, Emily, additional, Mohammed, Shehla, additional, Mononen, Tarja, additional, Mortenson, Megan E, additional, Moya, Graciela, additional, Nieuwint, Aggie W, additional, Ordulu, Zehra, additional, Parkash, Sandhya, additional, Pauker, Susan P, additional, Pereira, Shahrin, additional, Perrin, Danielle, additional, Phelan, Katy, additional, Aguilar, Raul E Piña, additional, Poddighe, Pino J, additional, Pregno, Giulia, additional, Raskin, Salmo, additional, Reis, Linda, additional, Rhead, William, additional, Rita, Debra, additional, Renkens, Ivo, additional, Roelens, Filip, additional, Ruliera, Jayla, additional, Rump, Patrick, additional, Schilit, Samantha L P, additional, Shaheen, Ranad, additional, Sparkes, Rebecca, additional, Spiegel, Erica, additional, Stevens, Blair, additional, Stone, Matthew R, additional, Tagoe, Julia, additional, Thakuria, Joseph V, additional, van Bon, Bregje W, additional, van de Kamp, Jiddeke, additional, van Der Burgt, Ineke, additional, van Essen, Ton, additional, van Ravenswaaij-Arts, Conny M, additional, van Roosmalen, Markus J, additional, Vergult, Sarah, additional, Volker-Touw, Catharina M L, additional, Warburton, Dorothy P, additional, Waterman, Matthew J, additional, Wiley, Susan, additional, Wilson, Anna, additional, Yerena-de Vega, Maria de la Concepcion A, additional, Zori, Roberto T, additional, Levy, Brynn, additional, Brunner, Han G, additional, de Leeuw, Nicole, additional, Kloosterman, Wigard P, additional, Thorland, Erik C, additional, Morton, Cynthia C, additional, Gusella, James F, additional, and Talkowski, Michael E, additional

Published
2016
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29. Exocytosis of polyubiquitinated proteins in bortezomib-resistant leukemia cells: a role for MARCKS in acquired resistance to proteasome inhibitors

Author

Franke, Niels E., primary, Kaspers, Gertjan L., additional, Assaraf, Yehuda G., additional, van Meerloo, Johan, additional, Niewerth, Denise, additional, Kessler, Floortje L., additional, Poddighe, Pino J., additional, Kole, Jeroen, additional, Smeets, Serge J., additional, Ylstra, Bauke, additional, Bi, Chonglei, additional, Chng, Wee Joo, additional, Horton, Terzah M., additional, Menezes, Rene X., additional, Musters, Renée J.P., additional, Zweegman, Sonja, additional, Jansen, Gerrit, additional, and Cloos, Jacqueline, additional

Published
2016
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31. Marcks Marks Resistance to Proteasome Inhibitors: Exocytosis of Polyubiquitinated Proteins in Bortezomib-Resistant Leukemia Cells

Author

Franke, Niels, primary, Kaspers, Gertjan J.L., additional, Assaraf, Yehuda G, additional, Van Meerloo, Johan, additional, Niewerth, Denise, additional, Horton, Terzah M., additional, Chng, Wee Joo, additional, Bi, Chonglei, additional, Menezes, Rene X., additional, Musters, Renée J., additional, Poddighe, Pino J., additional, Kessler, Floortje, additional, Smeets, Serge, additional, Ylstra, Bauke, additional, Zweegman, Sonja, additional, Jansen, Gerrit, additional, and Cloos, Jacqueline, additional

Published
2015
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33. Structural and numerical changes of chromosome X in patients with esophageal atresia

Author

Brosens, Erwin, primary, de Jong, Elisabeth M, additional, Barakat, Tahsin Stefan, additional, Eussen, Bert H, additional, D'haene, Barbara, additional, De Baere, Elfride, additional, Verdin, Hannah, additional, Poddighe, Pino J, additional, Galjaard, Robert-Jan, additional, Gribnau, Joost, additional, Brooks, Alice S, additional, Tibboel, Dick, additional, and de Klein, Annelies, additional

Published
2014
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34. Flow Cytometry Is Highly Predictive In Excluding Myelodysplastic Syndromes In Patients With Indeterminable Cytopenia: A Prospective Analysis Of 316 Patients

Author

Cremers, Eline M.P., primary, Westers, Theresia M, additional, Alhan, Canan, additional, Wondergem, Marielle J., additional, Poddighe, Pino J., additional, Cali, Claudia, additional, Schouten, C.W.M., additional, Ossenkoppele, Gert J., additional, and Van de Loosdrecht, Arjan A., additional

Published
2013
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35. 5q11.2 deletion in a patient with tracheal agenesis

Author

de Jong, Elisabeth M, primary, Douben, Hannie, additional, Eussen, Bert H, additional, Felix, Janine F, additional, Wessels, Marja W, additional, Poddighe, Pino J, additional, Nikkels, Peter G J, additional, de Krijger, Ronald R, additional, Tibboel, Dick, additional, and de Klein, Annelies, additional

Published
2010
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36. Unbalanced der(5)t(5;20) translocation associated with megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalus

Author

Verkerk, Annemieke J.M.H., primary, Schot, Rachel, additional, van Waterschoot, Laura, additional, Douben, Hannie, additional, Poddighe, Pino J., additional, Lequin, Maarten H., additional, de Vries, Linda S., additional, Terhal, Paulien, additional, Hahnemann, Johanne M.D., additional, de Coo, Irenaeus F.M., additional, de Wit, Marie-Claire Y., additional, Wafelman, Leontien S., additional, Garavelli, Livia, additional, Dobyns, William B., additional, Van der Spek, Peter J., additional, de Klein, Annelies, additional, and Mancini, Grazia M.S., additional

Published
2010
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38. Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report

Author

de Vree, Paula JP, primary, Simon, Marleen EH, additional, van Dooren, Marieke F, additional, Stoevelaar, Gerda HT, additional, Hilkmann, José TW, additional, Rongen, Michel A, additional, Huijbregts, Gido CM, additional, Verkerk, Annemieke JMH, additional, and Poddighe, Pino J, additional

Published
2009
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39. Numerical aberrations of chromosome 1 in cervical intraepithelial neoplasia are strongly associated with infection with high‐risk human papillomavirus types

Author

Bulten, Johan, primary, Melchers, Willem JG, additional, Kooy‐Smits, Maria M, additional, de Wilde, Peter CM, additional, Poddighe, Pino J, additional, Robben, Johanna CM, additional, Macville, Merryn VE, additional, Massuger, Leon FAG, additional, Bakkers, Judith MJE, additional, and Hanselaar, Antonius GJM, additional

Published
2002
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40. Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-transretinoic acid

Author

Verhagen, Han J.M.P., Smit, Marjon A., Rutten, Arjo, Denkers, Fedor, Poddighe, Pino J., Merle, Pauline A., Ossenkoppele, Gert J., and Smit, Linda

Abstract

Enhanced expression of ecotropic viral integration site 1 (EVI-1) occurs in ∼10% of acute myeloid leukemia (AML) patients and is associated with a very poor disease outcome. Patients with EVI-1–positive AML have poor initial responses to chemotherapy and high relapse rates, indicating an urgent need for alternative treatment strategies improving clinical outcome for these patients. Because treatment of acute promyelocytic patients with all-transretinoic acid (ATRA) has improved the survival of these patients substantially, we investigated whether ATRA might also be effective for the subgroup of AML patients with EVI-1 overexpression. Here, we show that a substantial part of the EVI-1–positive AML cases respond to ATRA by induction of differentiation and decreased clonogenic capacity of myeloid blasts. Most importantly, we demonstrate that in vivo treatment of primary EVI-1–positive AML with ATRA leads to a significant reduction in leukemic engraftment. Altogether, our results show that a considerable part of the EVI-1–positive primary AML cases are sensitive to ATRA, suggesting that combining ATRA with the currently used conventional chemotherapy might be a promising treatment strategy decreasing relapse rates and enhancing complete remissions in this poor prognostic subgroup of AML patients.

Published
2016
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46. Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with patient congenital anomalies.

Author

van der Veken, Lars T., Dieleman, Marianne M. J., Douben, Hannie, van de Brug, Judith C., van de Graaf, Raoul, Hoogeboom, A. Jeannette M., Poddighe, Pino J., and de Klein, Annelies

Subjects
GENETIC research, CHROMOSOMES, HUMAN abnormalities, GENETIC disorders, CELL nuclei, KARYOKINESIS, CRYPTORCHISM, DYSPLASIA, CONNECTIVE tissue cells, CROSSING over (Genetics)
Abstract

Background: Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Results: We report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BACprobes located in the region indicated the presence of 6 signals on the r(18) chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy. Conclusions: We report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11. [ABSTRACT FROM AUTHOR]

Published
2010
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47. Abnormalities of chromosome 1p/q are highly associated with chromosome 13/13q deletions and are an adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma.

Author

Ka Lung Wu, Beverloo, Berna, Lokhorst, Henk M., Segeren, Christine M., van der Holt, Bronno, Steijaert, Monique M., Westveer, Petra H., Poddighe, Pino J., Verhoef, Gregor E., and Sonneveld, Pieter

Subjects
CHROMOSOME abnormalities, MULTIPLE myeloma, B cell lymphoma, CYTOGENETICS, PROGNOSIS, DRUG therapy
Abstract

The prognostic value of chromosomal abnormalities was studied in untreated multiple myeloma patients who were registered into a prospective randomised multicentre phase 3 study for intensified treatment (HOVON24). A total of 453 patients aged less than 66 years with stage II and III A/B disease were registered in the clinical study. Cytogenetic analysis was introduced as a standard diagnostic assay in 1998. It was performed at diagnosis in 160 patients and was successful in 137/160 patients (86%). An abnormal karyotype was observed in 53/137 (39%) of the patients. Abnormalities of chromosome 1p and 1q were found in 19 (36% of patients with an abnormal karyotype) and 21 patients (40%). There was a strong association between chromosome 1p and/or 1q abnormalities and deletion of chromosome 13 or 13q ( n = 27, P < 0·001). Patients with karyotypic abnormalities had a significantly shorter overall survival (OS) than patients with normal karyotypes. Complex abnormalities, hypodiploidy, chromosome 1p abnormalities, chromosome 1q abnormalities, and chromosome 13 abnormalities were associated with inferior OS on univariate analysis, as well as after adjustment for other prognostic factors. In conclusion, chromosome 13 abnormalities and chromosome 1p and/or 1q abnormalities were highly associated, and are risk factors for poor outcome after intensive therapy in multiple myeloma. [ABSTRACT FROM AUTHOR]

Published
2007
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48. Reduced frequencies and functional impairment of dendritic cell subsets and non-classical monocytes in myelodysplastic syndromes.

Author

Van Leeuwen-Kerkhoff N, Westers TM, Poddighe PJ, Povoleri GAM, Timms JA, Kordasti S, De Gruijl TD, and Van de Loosdrecht AA

Subjects
Bone Marrow pathology, Dendritic Cells, Humans, Lymphocyte Activation, Monocytes, Myelodysplastic Syndromes pathology
Abstract

In myelodysplastic syndromes (MDS) the immune system is involved in pathogenesis as well as in disease progression. Dendritic cells (DC) are key players of the immune system by serving as regulators of immune responses. Their function has been scarcely studied in MDS and most of the reported studies didn't investigate naturally occurring DC subsets. Therefore, we here examined the frequency and function of DC subsets and slan+ non-classical monocytes in various MDS risk groups. Frequencies of DC as well as of slan+ monocytes were decreased in MDS bone marrow compared to normal bone marrow samples. Transcriptional profiling revealed down-regulation of transcripts related to pro-inflammatory pathways in MDS-derived cells as compared to normal bone marrow. Additionally, their capacity to induce T-cell proliferation was impaired. Multidimensional mass cytometry showed that whereas healthy donor-derived slan+ monocytes supported Th1/Th17/Treg differentiation/expansion their MDS-derived counterparts also mediated substantial Th2 expansion. Our findings point to a role for an impaired ability of DC subsets to adequately respond to cellular stress and DNA damage in the immune escape and progression of MDS. As such, it paves the way toward potential novel immunotherapeutic interventions.

Published
2022
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49. Ixazomib-Thalidomide-low dose dexamethasone induction followed by maintenance therapy with ixazomib or placebo in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplantation; results from the randomized phase II HOVON-126/NMSG 21.13 trial.

Author

Zweegman S, Stege CAM, Haukas E, Schjesvold FH, Levin MD, Waage A, Leys RBL, Klein SK, Szatkowski D, Axelsson P, Hieu Do T, Knut-Bojanowska D, van der Spek E, Svirskaite A, Klostergaard A, Salomo M, Blimark C, Ypma PF, Mellqvist UH, Poddighe PJ, Stevens-Kroef M, van de Donk NWCJ, Sonneveld P, Hansson M, van der Holt B, and Abildgaard N

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, Boron Compounds, Bortezomib therapeutic use, Dexamethasone therapeutic use, Glycine analogs & derivatives, Humans, Stem Cell Transplantation, Thalidomide therapeutic use, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
Published
2020
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50. Thrombomodulin-expressing monocytes are associated with low-risk features in myelodysplastic syndromes and dampen excessive immune activation.

Author

van Leeuwen-Kerkhoff N, Westers TM, Poddighe PJ, de Gruijl TD, Kordasti S, and van de Loosdrecht AA

Subjects
Bone Marrow, Disease Progression, Humans, Thrombomodulin genetics, Monocytes, Myelodysplastic Syndromes
Abstract

The bone marrow of patients with low-risk myelodysplastic syndromes (MDS) is often an inflammatory environment and associated with an active cellular immune response. An active immune response generally contributes to antitumor responses and may prevent disease progression. However, chronic immune stimulation can also induce cell stress, DNA damage and contribute to the pathogenesis of MDS. The protective mechanisms against excessive immune activation are therefore an important aspect of the pathophysiology of MDS and characterizing them may help us to better understand the fine balance between protective and destabilizing inflammation in lower-risk disease. In this study we investigated the role of thrombomodulin (CD141/BDCA-3) expression, a molecule with anti-inflammatory properties, on monocytes in the bone marrow and peripheral blood of MDS patients in different risk groups. Patient-derived classical monocytes showed high expression levels of thrombomodulin, whereas monocytes from healthy donors hardly expressed any thrombomodulin. The presence of thrombomodulin on monocytes from MDS patients correlated with lower-risk disease groups and better overall and leukemia-free survival. Using multidimensional mass cytometry, in an in-vitro setting, we showed that thrombomodulin-positive monocytes could polarize naïve T cells toward cell clusters which are closer to T helper type 2 and T regulatory cell phenotypes and less likely to contribute to effective immune surveillance. In conclusion, the expression of thrombomodulin on classical monocytes is a favorable and early prognostic marker in patients with low-risk MDS and may represent a new mechanism in the protection against disproportionate immune activation., (Copyright© 2020 Ferrata Storti Foundation.)

Published
2020
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