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196 results on '"Cave H."'

1. CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951

Author

Sirvent, N., Suciu, S., De Moerloose, B., Ferster, A., Mazingue, F., Plat, G., Yakouben, K., Uyttebroeck, A., Paillard, C., Costa, V., Simon, P., Pluchart, C., Poirée, M., Minckes, O., Millot, F., Freycon, C., Maes, P., Hoyoux, C., Cavé, H., Rohrlich, P., Bertrand, Y., and Benoit, Y.

Published
2021
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3. The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia

Author

Kulp, M, Siemund, A, Larghero, P, Dietz, A, Alten, J, Cario, G, Eckert, C, Caye-Eude, A, Cave, H, Bardini, M, Cazzaniga, G, De Lorenzo, P, Valsecchi, M, Diehl, L, Bonig, H, Meyer, C, Marschalek, R, Kulp M., Siemund A. L., Larghero P., Dietz A., Alten J., Cario G., Eckert C., Caye-Eude A., Cave H., Bardini M., Cazzaniga G., De Lorenzo P., Valsecchi M. G., Diehl L., Bonig H., Meyer C., Marschalek R., Kulp, M, Siemund, A, Larghero, P, Dietz, A, Alten, J, Cario, G, Eckert, C, Caye-Eude, A, Cave, H, Bardini, M, Cazzaniga, G, De Lorenzo, P, Valsecchi, M, Diehl, L, Bonig, H, Meyer, C, Marschalek, R, Kulp M., Siemund A. L., Larghero P., Dietz A., Alten J., Cario G., Eckert C., Caye-Eude A., Cave H., Bardini M., Cazzaniga G., De Lorenzo P., Valsecchi M. G., Diehl L., Bonig H., Meyer C., and Marschalek R.

Abstract

The most frequent genetic aberration leading to infant ALL (iALL) is the chromosomal translocation t(4;11), generating the fusion oncogenes KMT2A:AFF1 and AFF1:KMT2A, respectively. KMT2A-r iALL displays a dismal prognosis through high relapse rates and relapse-associated mortality. Relapse occurs frequently despite ongoing chemotherapy and without the accumulation of secondary mutations. A rational explanation for the observed chemo-resistance and satisfactory treatment options remain to be elucidated. We found that elevated ICOSLG expression level at diagnosis was associated with inferior event free survival (EFS) in a cohort of 43 patients with t(4;-11) iALL and that a cohort of 18 patients with iALL at relapse displayed strongly increased ICOSLG expression. Furthermore, co-culturing t(4;11) ALL cells (ICOSLGhi) with primary T-cells resulted in the development of Tregs. This was impaired through treatment with a neutralizing ICOSLG antibody. These findings imply ICOSLG (1) as a relapse-predicting biomarker, and (2) as a therapeutic target involved in a potential immune evasion relapse-mechanism of infant t(4;11) ALL.

Published
2022

4. Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse

Author

Antic, Z, Yu, J, Bornhauser, B, Lelieveld, S, van der Ham, C, van Reijmersdal, S, Morgado, L, Elitzur, S, Bourquin, J, Cazzaniga, G, Eckert, C, Camos, M, Sutton, R, Cave, H, Moorman, A, Sonneveld, E, Geurts van Kessel, A, van Leeuwen, F, Hoogerbrugge, P, Waanders, E, Kuiper, R, Antic Z., Yu J., Bornhauser B. C., Lelieveld S. H., van der Ham C. G., van Reijmersdal S. V., Morgado L., Elitzur S., Bourquin J. -P., Cazzaniga G., Eckert C., Camos M., Sutton R., Cave H., Moorman A. V., Sonneveld E., Geurts van Kessel A., van Leeuwen F. N., Hoogerbrugge P. M., Waanders E., Kuiper R. P., Antic, Z, Yu, J, Bornhauser, B, Lelieveld, S, van der Ham, C, van Reijmersdal, S, Morgado, L, Elitzur, S, Bourquin, J, Cazzaniga, G, Eckert, C, Camos, M, Sutton, R, Cave, H, Moorman, A, Sonneveld, E, Geurts van Kessel, A, van Leeuwen, F, Hoogerbrugge, P, Waanders, E, Kuiper, R, Antic Z., Yu J., Bornhauser B. C., Lelieveld S. H., van der Ham C. G., van Reijmersdal S. V., Morgado L., Elitzur S., Bourquin J. -P., Cazzaniga G., Eckert C., Camos M., Sutton R., Cave H., Moorman A. V., Sonneveld E., Geurts van Kessel A., van Leeuwen F. N., Hoogerbrugge P. M., Waanders E., and Kuiper R. P.

Abstract

Introduction: One-quarter of the relapses in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occur very early (within 18 months, before completion of treatment), and prognosis in these patients is worse compared to cases that relapse after treatment has ended. Methods: In this study, we performed a genomic analysis of diagnosis–relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy. Results: We observed a dynamic clonal evolution in all cases, with relapse almost exclusively originating from a subclone at diagnosis. We identified several driver mutations that may have influenced the outgrowth of a minor clone at diagnosis to become the major clone at relapse. For example, a minimal residual disease (MRD)-based standard-risk patient with ETV6-RUNX1-positive leukemia developed a relapse from a TP53-mutated subclone after loss of the wildtype allele. Furthermore, two patients with TCF3-PBX1-positive leukemia that developed a very early relapse carried E1099K WHSC1 mutations at diagnosis, a hotspot mutation that was recurrently encountered in other very early TCF3-PBX1-positive leukemia relapses as well. In addition to alterations in known relapse drivers, we found two cases with truncating mutations in the cohesin gene RAD21. Conclusion: Comprehensive genomic characterization of diagnosis–relapse pairs shows that very early relapses in BCP-ALL frequently arise from minor subclones at diagnosis. A detailed understanding of the therapeutic pressure driving these events may aid the development of improved therapies.

Published
2022

6. Clinical characteristics and outcomes of B-ALL with ZNF384 rearrangements: a retrospective analysis by the Ponte di Legno Childhood ALL Working Group

Author

Hirabayashi, S, Butler, E, Ohki, K, Kiyokawa, N, Bergmann, A, Moricke, A, Boer, J, Cave, H, Cazzaniga, G, Yeoh, A, Sanada, M, Imamura, T, Inaba, H, Mullighan, C, Loh, M, Noren-Nystrom, U, Pastorczak, A, Shih, L, Zaliova, M, Pui, C, Haas, O, Harrison, C, Moorman, A, Manabe, A, Hirabayashi S., Butler E. R., Ohki K., Kiyokawa N., Bergmann A. K., Moricke A., Boer J. M., Cave H., Cazzaniga G., Yeoh A. E. J., Sanada M., Imamura T., Inaba H., Mullighan C., Loh M. L., Noren-Nystrom U., Pastorczak A., Shih L. -Y., Zaliova M., Pui C. -H., Haas O. A., Harrison C. J., Moorman A. V., Manabe A., Hirabayashi, S, Butler, E, Ohki, K, Kiyokawa, N, Bergmann, A, Moricke, A, Boer, J, Cave, H, Cazzaniga, G, Yeoh, A, Sanada, M, Imamura, T, Inaba, H, Mullighan, C, Loh, M, Noren-Nystrom, U, Pastorczak, A, Shih, L, Zaliova, M, Pui, C, Haas, O, Harrison, C, Moorman, A, Manabe, A, Hirabayashi S., Butler E. R., Ohki K., Kiyokawa N., Bergmann A. K., Moricke A., Boer J. M., Cave H., Cazzaniga G., Yeoh A. E. J., Sanada M., Imamura T., Inaba H., Mullighan C., Loh M. L., Noren-Nystrom U., Pastorczak A., Shih L. -Y., Zaliova M., Pui C. -H., Haas O. A., Harrison C. J., Moorman A. V., and Manabe A.

Published
2021

7. Favorable outcome of NUTM1-rearranged infant and pediatric B cell precursor acute lymphoblastic leukemia in a collaborative international study

Author

Boer, J, Valsecchi, M, Hormann, F, Antic, Z, Zaliova, M, Schwab, C, Cazzaniga, G, Arfeuille, C, Cave, H, Attarbaschi, A, Strehl, S, Escherich, G, Imamura, T, Ohki, K, Gruber, T, Sutton, R, Pastorczak, A, Lammens, T, Lambert, F, Li, C, Carrillo de Santa Pau, E, Hoffmann, S, Moricke, A, Harrison, C, Den Boer, M, De Lorenzo, P, Stam, R, Bergmann, A, Pieters, R, Boer J. M., Valsecchi M. G., Hormann F. M., Antic Z., Zaliova M., Schwab C., Cazzaniga G., Arfeuille C., Cave H., Attarbaschi A., Strehl S., Escherich G., Imamura T., Ohki K., Gruber T. A., Sutton R., Pastorczak A., Lammens T., Lambert F., Li C. K., Carrillo de Santa Pau E., Hoffmann S., Moricke A., Harrison C. J., Den Boer M. L., De Lorenzo P., Stam R. W., Bergmann A. K., Pieters R., Boer, J, Valsecchi, M, Hormann, F, Antic, Z, Zaliova, M, Schwab, C, Cazzaniga, G, Arfeuille, C, Cave, H, Attarbaschi, A, Strehl, S, Escherich, G, Imamura, T, Ohki, K, Gruber, T, Sutton, R, Pastorczak, A, Lammens, T, Lambert, F, Li, C, Carrillo de Santa Pau, E, Hoffmann, S, Moricke, A, Harrison, C, Den Boer, M, De Lorenzo, P, Stam, R, Bergmann, A, Pieters, R, Boer J. M., Valsecchi M. G., Hormann F. M., Antic Z., Zaliova M., Schwab C., Cazzaniga G., Arfeuille C., Cave H., Attarbaschi A., Strehl S., Escherich G., Imamura T., Ohki K., Gruber T. A., Sutton R., Pastorczak A., Lammens T., Lambert F., Li C. K., Carrillo de Santa Pau E., Hoffmann S., Moricke A., Harrison C. J., Den Boer M. L., De Lorenzo P., Stam R. W., Bergmann A. K., and Pieters R.

Published
2021

9. Correction: Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1 (Leukemia, (2019), 33, 8, (1910-1922), 10.1038/s41375-019-0413-0)

Author

Pfeifer H., Pfeifer, H, Cazzaniga, G, van der Velden, V, Cayuela, J, Schafer, B, Spinelli, O, Akiki, S, Avigad, S, Bendit, I, Borg, K, Cave, H, Elia, L, Reshmi, S, Gerrard, G, Hayette, S, Hermanson, M, Juh, A, Jurcek, T, Chillon, M, Homburg, C, Martinelli, G, Kairisto, V, Lange, T, Lion, T, Mueller, M, Pane, F, Rai, L, Damm-Welk, C, Sacha, T, Schnittger, S, Touloumenidou, T, Valerhaugen, H, Vandenberghe, P, Zuna, J, Serve, H, Herrmann, E, Markovic, S, van Dongen, J, Ottmann, O, Pfeifer H., Cazzaniga G., van der Velden V. H. J., Cayuela J. M., Schafer B., Spinelli O., Akiki S., Avigad S., Bendit I., Borg K., Cave H., Elia L., Reshmi S. C., Gerrard G., Hayette S., Hermanson M., Juh A., Jurcek T., Chillon M. C., Homburg C., Martinelli G., Kairisto V., Lange T., Lion T., Mueller M. C., Pane F., Rai L., Damm-Welk C., Sacha T., Schnittger S., Touloumenidou T., Valerhaugen H., Vandenberghe P., Zuna J., Serve H., Herrmann E., Markovic S., van Dongen J. J. M., Ottmann O. G., Pfeifer H., Pfeifer, H, Cazzaniga, G, van der Velden, V, Cayuela, J, Schafer, B, Spinelli, O, Akiki, S, Avigad, S, Bendit, I, Borg, K, Cave, H, Elia, L, Reshmi, S, Gerrard, G, Hayette, S, Hermanson, M, Juh, A, Jurcek, T, Chillon, M, Homburg, C, Martinelli, G, Kairisto, V, Lange, T, Lion, T, Mueller, M, Pane, F, Rai, L, Damm-Welk, C, Sacha, T, Schnittger, S, Touloumenidou, T, Valerhaugen, H, Vandenberghe, P, Zuna, J, Serve, H, Herrmann, E, Markovic, S, van Dongen, J, Ottmann, O, Pfeifer H., Cazzaniga G., van der Velden V. H. J., Cayuela J. M., Schafer B., Spinelli O., Akiki S., Avigad S., Bendit I., Borg K., Cave H., Elia L., Reshmi S. C., Gerrard G., Hayette S., Hermanson M., Juh A., Jurcek T., Chillon M. C., Homburg C., Martinelli G., Kairisto V., Lange T., Lion T., Mueller M. C., Pane F., Rai L., Damm-Welk C., Sacha T., Schnittger S., Touloumenidou T., Valerhaugen H., Vandenberghe P., Zuna J., Serve H., Herrmann E., Markovic S., van Dongen J. J. M., and Ottmann O. G.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

10. Syndrome neurofibromatose type 1-Noonan : étude rétrospective de 26- patients

Author

Bessis, D., Poujade, L., Pacot, L., Vidaud, D., Cave, H., Genevieve, D., and Willems, M.

Abstract

Le syndrome neurofibromatose de type 1 (NF1)-Noonan constitue une variante phénotypique rare de NF1 caractérisée par l’association de particularités morphologiques faciales de type Noonan à une NF1. Sa prévalence et ses manifestations cliniques restent peu évaluées. Aucune recommandation en termes de prise en charge médicale spécifique n’est établie, à l’inverse des autres RASopathies.

Published
2024
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11. Outcome of children with hypodiploid acute lymphoblastic leukemia: A retrospective multinational study

Author

Pui, C, Rebora, P, Schrappe, M, Attarbaschi, A, Baruchel, A, Basso, G, Cave, H, Elitzur, S, Koh, K, Liu, H, Paulsson, K, Pieters, R, Silverman, L, Stary, J, Vora, A, Yeoh, A, Harrison, C, Valsecchi, M, Pui C. -H., Rebora P., Schrappe M., Attarbaschi A., Baruchel A., Basso G., Cave H., Elitzur S., Koh K., Liu H. -C., Paulsson K., Pieters R., Silverman L. B., Stary J., Vora A., Yeoh A., Harrison C. J., Valsecchi M. G., Pui, C, Rebora, P, Schrappe, M, Attarbaschi, A, Baruchel, A, Basso, G, Cave, H, Elitzur, S, Koh, K, Liu, H, Paulsson, K, Pieters, R, Silverman, L, Stary, J, Vora, A, Yeoh, A, Harrison, C, Valsecchi, M, Pui C. -H., Rebora P., Schrappe M., Attarbaschi A., Baruchel A., Basso G., Cave H., Elitzur S., Koh K., Liu H. -C., Paulsson K., Pieters R., Silverman L. B., Stary J., Vora A., Yeoh A., Harrison C. J., and Valsecchi M. G.

Abstract

PURPOSE We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly (P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogenei

Published
2019

15. Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1 (vol 32, pg 345, 2019)

Author

Pfeifer, H., Cazzaniga, G., Velden, V.H.J. van der, Cayuela, J.M., Schafer, B., Spinelli, O., Akiki, S., Avigad, S., Bendit, I., Borg, K., Cave, H., Elia, L., Reshmi, S.C., Gerrard, G., Hayette, S., Hermanson, M., Juh, A., Jurcek, T., Chillon, M.C., Homburg, C., Martinelli, G., Kairisto, V., Lange, T., Lion, T., Mueller, M.C., Pane, F., Rai, L., Damm-Welk, C., Sacha, T., Schnittger, S., Touloumenidou, T., Valerhaugen, H., Vandenberghe, P., Zuna, J., Serve, H., Herrmann, E., Markovic, S., Dongen, J.J.M. van, and Ottmann, O.G.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

18. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study

Author

Bowman P., Sulen A., Barbetti F., Beltrand J., Svalastoga P., Codner E., Tessmann E. H., Juliusson P. B., Skrivarhaug T., Pearson E. R., Flanagan S. E., Babiker T., Thomas N. J., Shepherd M. H., Ellard S., Klimes I., Szopa M., Polak M., Iafusco D., Hattersley A. T., Njolstad P. R., Aisenberg J., Akkurt I., Abdul-Latif H., Al-Abdullah A., Barak L., Van Den Bergh J., Bertrand A. -M., Bizzarri C., Bonfanti R., Bruel H., Burrows A., Cadario F., Cameron F. J., Carson D., Cartigny M., Cauvin V., Cave H., Chakera A., Chetan R., Chiari G., Couch B., Coutant R., Cummings E., Dankovcikova A., Davis L., Deiss D., Delvecchio M., Faleschini E., Fauret A. -L., Finn R., Ford T., Franco E. D., Gallen B. D., Gasperikova D., Guntamukkala P., Hakeem V., Hasegawa S., Hathout E. H., Heffernan E., Hill D., Ho J., Hoarau M., Holl R., Hoddinott R., Houghton J., Howard N., Hughes N., Hunter I., Hogasen A. K., Kuulasmaa H., Ioacara S., Iotova V., Irgens H., Jaap A., Jones K., Kapellen T., Kaufman E., Klinge A., Klupa T., Krishnaswamy R., Lafferty T., LeGault L., Lambert P., Malecki M. T., Malievsky O., Mathew R., Mathews F., McVie R., Menzel U., Metz C., Meulen J. V. D., Modgil G., Mul D., Muther S., Nuboer R., O'Connell S. M., O'Riordan S., Palko M., Patel K. A., Pesavento R., Piccinno E., Pillai J. K., Pruhova S., Punthakee Z., Rabbone I., Raile K., Rincon M., Rose D., Sanchez J., Sandereson S., Saxena V., Schebek M., Schmidt D., Shehadeh N., Shiels J. P. H., Silva J. M. C. L., Stanik J., Tinklin T., Tjora E., Tumini S., Tuomi T., Uehara A., Velde R. V. D., Vermeulen G., Visser U., Voorhoeve P., Walker J., Weill J., Weisner T., Werner A., Williams T., Woodhead H., oddegard R., Bowman, Pamela, Sulen, Åsta, Barbetti, Fabrizio, Beltrand, Jacque, Svalastoga, Pernille, Codner, Ethel, Tessmann, Ellen H, Juliusson, Petur B, Skrivarhaug, Torild, Pearson, Ewan R, Flanagan, Sarah E, Babiker, Tarig, Thomas, Nicholas J, Shepherd, Maggie H, Ellard, Sian, Klimes, Iwar, Szopa, Magdalena, Polak, Michel, Iafusco, Dario, Hattersley, Andrew T, Njølstad, Pål R, Aisenberg, Javier, Akkurt, Ilker, Abdul-Latif, Hussein, Al-Abdullah, Anee, Barak, Lubomir, Van Den Bergh, Joop, Bertrand, Anne-Marie, Bizzarri, Carla, Bonfanti, Riccardo, Bruel, Henri, Burrows, Anthony, Cadario, Francesco, Cameron, Fergus J., Carson, Denni, Cartigny, Maryse, Cauvin, Vittoria, Cave, Helene, Chakera, Ali, Chetan, Ravi, Chiari, Giovanni, Couch, Bob, Coutant, Régi, Cummings, Elizabeth, Dankovcikova, Adriana, Davis, Liz, Deiss, Dorothee, Delvecchio, Maurizio, Faleschini, Elena, Fauret, Anne-Laure, Finn, Roisin, Ford, Tamsin, Franco, Elisa De, Gallen, Bastian De, Gasperíková, Daniela, Guntamukkala, Padma, Hakeem, Vaseem, Hasegawa, Shinji, Hathout, Eba H., Heffernan, Emmeline, Hill, David, Ho, Josephine, Hoarau, Marie, Holl, Reinhard, Hoddinott, Rebecca, Houghton, Jane, Howard, Neville, Hughes, Natalie, Hunter, Ian, Høgåsen, Anne Kirsti, Kuulasmaa, Helena, Iocara, Sorin, Iotova, Violeta, Irgens, Henrik, Jaap, Alan, Jones, Kenneth, Kapellen, Thoma, Kaufman, Ellen, Klinge, Andrea, Klupa, Tomasz, Krishnaswamy, Ramaiyer, Lafferty, Tony, Legault, Laurent, Lambert, Paul, Malecki, Maciej T, Malievsky, Olag, Mathew, Revi, Mathews, France, Mcvie, Robert, Menzel, Ulrike, Metz, Chantale, Meulen, John Van Der, Modgil, Gita, Mul, Dick, Muther, Silvia, Nuboer, Roo, O'Connell, Susan M., O'Riordan, Stephen, Palko, Miroslav, Patel, Kashyap Amratlal, Pesavento, Roberta, Piccinno, Elvira, Pillai, Janani Kumaraguru, Pruhova, Stephanka, Punthakee, Zubin, Rabbone, Ivana, Raile, Klemen, Rincon, Marielisa, Rose, Danette, Sanchez, Janine, Sandereson, Susan, Saxena, Vinay, Schebek, Martin, Schmidt, Dorothee, Shehadeh, Naim, Shiels, Julian P. H., Silva, Jose M. C. L, Stanik, Juraj, Tinklin, Tracy, Tjora, Erling, Tumini, Stefano, Tuomi, Tiinamaija, Uehara, Akiko, Velde, Robert Van der, Vermeulen, Guido, Visser, Uma, Voorhoeve, Paul, Walker, Jan, Weill, Jaque, Weisner, Tobia, Werner, Andrea, Williams, Toni, Woodhead, Helen, Øddegård, Rønnaug, Bowman, P., Sulen, A., Barbetti, F., Beltrand, J., Svalastoga, P., Codner, E., Tessmann, E. H., Juliusson, P. B., Skrivarhaug, T., Pearson, E. R., Flanagan, S. E., Babiker, T., Thomas, N. J., Shepherd, M. H., Ellard, S., Klimes, I., Szopa, M., Polak, M., Iafusco, D., Hattersley, A. T., Njolstad, P. R., Aisenberg, J., Akkurt, I., Abdul-Latif, H., Al-Abdullah, A., Barak, L., Van Den Bergh, J., Bertrand, A. -M., Bizzarri, C., Bonfanti, R., Bruel, H., Burrows, A., Cadario, F., Cameron, F. J., Carson, D., Cartigny, M., Cauvin, V., Cave, H., Chakera, A., Chetan, R., Chiari, G., Couch, B., Coutant, R., Cummings, E., Dankovcikova, A., Davis, L., Deiss, D., Delvecchio, M., Faleschini, E., Fauret, A. -L., Finn, R., Ford, T., Franco, E. D., Gallen, B. D., Gasperikova, D., Guntamukkala, P., Hakeem, V., Hasegawa, S., Hathout, E. H., Heffernan, E., Hill, D., Ho, J., Hoarau, M., Holl, R., Hoddinott, R., Houghton, J., Howard, N., Hughes, N., Hunter, I., Hogasen, A. K., Kuulasmaa, H., Ioacara, S., Iotova, V., Irgens, H., Jaap, A., Jones, K., Kapellen, T., Kaufman, E., Klinge, A., Klupa, T., Krishnaswamy, R., Lafferty, T., Legault, L., Lambert, P., Malecki, M. T., Malievsky, O., Mathew, R., Mathews, F., Mcvie, R., Menzel, U., Metz, C., Meulen, J. V. D., Modgil, G., Mul, D., Muther, S., Nuboer, R., O'Connell, S. M., O'Riordan, S., Palko, M., Patel, K. A., Pesavento, R., Piccinno, E., Pillai, J. K., Pruhova, S., Punthakee, Z., Rabbone, I., Raile, K., Rincon, M., Rose, D., Sanchez, J., Sandereson, S., Saxena, V., Schebek, M., Schmidt, D., Shehadeh, N., Shiels, J. P. H., Silva, J. M. C. L., Stanik, J., Tinklin, T., Tjora, E., Tumini, S., Tuomi, T., Uehara, A., Velde, R. V. D., Vermeulen, G., Visser, U., Voorhoeve, P., Walker, J., Weill, J., Weisner, T., Werner, A., Williams, T., Woodhead, H., and Oddegard, R.

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Background: KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. Methods: In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA 1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817. Findings: 90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA 1c and sulfonylurea at all time points (ie, pre-transfer [for HbA 1c ], year 1, and most recent follow-up; n=64)—median HbA 1c was 8·1% (IQR 7·2–9·2; 65·0 mmol/mol [55·2–77·1]) before transfer to sulfonylureas, 5·9% (5·4–6·5; 41·0 mmol/mol [35·5–47·5]; p

Published
2018

19. Germline mutations of the CBL gene define a new genetic syndrome with predisposition to juvenile myelomonocytic leukaemia

Author

Perez, B., Mechinaud, F., Galambrun, C., Romdhane, N. Ben, Isidor, B., Philip, N., Derain-Court, J., Cassinat, B., Lachenaud, J., Kaltenbach, S., Salmon, A., Desiree, C., Pereira, S., Menot, M.L., Royer, N., Fenneteau, O., Baruchel, A., Chomienne, C., Verloes, A., and Cave, H.

Subjects
Chronic myelomonocytic leukemia -- Genetic aspects, Chronic myelomonocytic leukemia -- Risk factors, Chronic myelomonocytic leukemia -- Research, Gene mutations -- Research, Ubiquitin-proteasome system -- Genetic aspects, Ubiquitin-proteasome system -- Research, Health
Published
2010

22. Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases

Author

Kerr, B., Delrue, M.-A., Sigaudy, S., Perveen, R., Marche, M., Burgelin, I., Stef, M., Tang, B., Eden, O.B., OESullivan, J., De Sandre-Giovannoli, A., Reardon, W., Brewer, C., Bennett, C., Quarell, O., MECann, E., Donnai, D., Stewart, F., Hennekam, R., Cave, H., Verloes, A., Philip, N., Lacombe, D., Levy, N., Arveiler, B., and Black, G.

Subjects
Multiple abnormalities -- Genetic aspects, Multiple abnormalities -- Causes of, Multiple abnormalities -- Research, Gene mutations -- Analysis, Health
Published
2006

23. Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph plus ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1

Author

Pfeifer, H., Cazzaniga, G., van der Velden, V. H. J., Cayuele, J. M., Schafer, B., Spinelli, O., Akiki, S., Avigad, S., Bendit, I, Borg, K., Cave, H., Elia, L., Reshmi, S. C., Gerrard, G., Hayette, S., Hermansson, Monica, Juh, A., Jurcek, T., Chillon, M. C., Homburg, C., Martinelli, G., Kairisto, V, Langen, T., Lion, T., Mueller, M. C., Pane, F., Rai, L., Damm-Welk, C., Sacha, T., Schnittger, S., Touloumenidou, T., Valerhaugen, H., Vandenberghe, P., Zuna, J., Server, H., Herrmann, E., Markovic, S., van Dongen, J. J. M., Ottmann, O. G., Pfeifer, H., Cazzaniga, G., van der Velden, V. H. J., Cayuele, J. M., Schafer, B., Spinelli, O., Akiki, S., Avigad, S., Bendit, I, Borg, K., Cave, H., Elia, L., Reshmi, S. C., Gerrard, G., Hayette, S., Hermansson, Monica, Juh, A., Jurcek, T., Chillon, M. C., Homburg, C., Martinelli, G., Kairisto, V, Langen, T., Lion, T., Mueller, M. C., Pane, F., Rai, L., Damm-Welk, C., Sacha, T., Schnittger, S., Touloumenidou, T., Valerhaugen, H., Vandenberghe, P., Zuna, J., Server, H., Herrmann, E., Markovic, S., van Dongen, J. J. M., and Ottmann, O. G.

Abstract

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10(-3) and 36/67 (53%) and 53/67 (79%) at 10(-4)BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph + ALL.

Published
2019
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24. Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL-USP2 fusions

Author

Meyer, C, Lopes, BA, Caye-Eude, A, Cave, H, Arfeuille, C, Cuccuini, W, Sutton, R, Venn, NC, Oh, SH, Tsaur, G, Escherich, G, Feuchtinger, T, Kosasih, HJ, Khaw, SL, Ekert, PG, Pombo-de-Oliveira, MS, Bidet, A, Djahanschiri, B, Ebersberger, I, Zaliova, M, Zuna, J, Zermanova, Z, Juvonen, V, Gruemayer, RP, Fazio, G, Cazzaniga, G, Larghero, P, Emerenciano, M, Marschalek, R, Meyer, C, Lopes, BA, Caye-Eude, A, Cave, H, Arfeuille, C, Cuccuini, W, Sutton, R, Venn, NC, Oh, SH, Tsaur, G, Escherich, G, Feuchtinger, T, Kosasih, HJ, Khaw, SL, Ekert, PG, Pombo-de-Oliveira, MS, Bidet, A, Djahanschiri, B, Ebersberger, I, Zaliova, M, Zuna, J, Zermanova, Z, Juvonen, V, Gruemayer, RP, Fazio, G, Cazzaniga, G, Larghero, P, Emerenciano, M, and Marschalek, R

Published
2019

26. PF175 MULTICENTRE STANDARDIZATION OF MINIMAL RESIDUAL DISEASE DETECTION AND QUANTITATION USING THE EUROCLONALITY-NGS ASSAY

Author

Svaton, M., primary, Fronkova, E., additional, Kotrova, M., additional, Reigl, T., additional, Caye, A., additional, de Bie, M., additional, Genuardi, E., additional, Jelinkova, H., additional, Lim, E.H., additional, Nishijima, D., additional, Pal, K., additional, Salemi, D., additional, Sarasquete, M.E., additional, Songia, S., additional, Tosi, M., additional, Villarese, P., additional, Wakeman, S., additional, Cave, H., additional, Cazzaniga, G., additional, Ferrero, S., additional, Garcia Sanz, R., additional, Hancock, J., additional, Macintyre, E., additional, Plevova, K., additional, Sanada, M., additional, Santoro, A., additional, Spinelli, O., additional, van der Velden, V.H., additional, Yeoh, A.E. J., additional, Langerak, A.W., additional, Darzentas, N., additional, Brüggemann, M., additional, and Trka, J., additional

Published
2019
Full Text
View/download PDF

27. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C., Burmeister, T., Groeger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-de-Oliveira, M. S., Blunck, C. Barbieri, Lopes, B. Almeida, Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Abascal, L. Corral, van der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., zur Stadt, U., Lentes, J., Goehring, G., Kustanovich, A., Aleinikova, O., Schafer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., van den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Moericke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Gruemayer, R., Sedek, L., Szczepanski, T., Caye, A., Suarez, L., Cave, H., Marschalek, R., Meyer, C., Burmeister, T., Groeger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-de-Oliveira, M. S., Blunck, C. Barbieri, Lopes, B. Almeida, Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Abascal, L. Corral, van der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., zur Stadt, U., Lentes, J., Goehring, G., Kustanovich, A., Aleinikova, O., Schafer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., van den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Moericke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Gruemayer, R., Sedek, L., Szczepanski, T., Caye, A., Suarez, L., Cave, H., and Marschalek, R.

Published
2018

28. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study

Author

Bowman, P, Sulen, A, Barbetti, F, Beltrand, J, Svalastoga, P, Codner, E, Tessmann, EH, Juliusson, PB, Skrivarhaug, T, Pearson, ER, Flanagan, SE, Babiker, T, Thomas, NJ, Shepherd, MH, Ellard, S, Klimes, I, Szopa, M, Polak, M, Iafusco, D, Hattersley, AT, Njolstad, PR, Houghton, J, Patel, KA, Mathews, F, De Franco, E, Ford, T, Pillai, JK, Finn, R, Chakera, A, Iotova, V, Malecki, MT, Klupa, T, Gasperikova, D, Stanik, J, Barak, L, Dankovcikova, A, Palko, M, Walker, J, Visser, U, Howard, N, Lafferty, T, Cummings, E, Guntamukkala, P, Rose, D, Hughes, N, Couch, B, Punthakee, Z, Van der Meulen, J, LeGault, L, Sanderson, S, Krishnaswamy, R, Ho, J, Modgil, G, Lambert, P, Shield, JPH, Hoddinott, R, Burrows, A, Chetan, R, Hakeem, V, Werner, A, Muther, S, Deiss, D, Raile, K, Weisner, T, Kapellen, T, Akkurt, I, Menzel, U, Klinge, A, Schmidt, D, Heffernan, E, Carson, D, Uehara, A, Hasegawa, S, Kuulasmaa, H, Tuomi, T, Vermeulen, G, Mul, D, Jaap, A, Hill, D, Hunter, I, Rincon, M, McVie, R, Williams, T, Saxena, V, Al-Abdullah, A, Tinklin, T, Kaufman, E, Davis, L, O'Riordan, S, O'Connell, SM, Holl, R, Schebek, M, De Gallen, B, Voorhoeve, P, Malievsky, O, Mathew, R, Abdul-Latif, H, Aisenberg, J, Ioacara, S, Cameron, FJ, Sanchez, J, Jones, K, Van der Velde, R, Van den Bergh, J, Woodhead, H, Tjora, E, Irgens, H, Hogåsen, AK, Odegard, R, Hathout, EH, Nuboer, R, Pruhova, S, Shehadeh, N, Silva, JMCL, Cave, H, Fauret, A-L, Hoarau, M, Coutant, R, Metz, C, Bertrand, A-M, Bruel, H, Cartigny, M, Weill, J, Bizzarri, C, Bonfanti, R, Cadario, F, Cauvin, V, Chiari, G, Delvecchio, M, Piccinno, E, Faleschini, E, Pesavento, R, Rabbone, I, Tumini, S, Bowman, P, Sulen, A, Barbetti, F, Beltrand, J, Svalastoga, P, Codner, E, Tessmann, EH, Juliusson, PB, Skrivarhaug, T, Pearson, ER, Flanagan, SE, Babiker, T, Thomas, NJ, Shepherd, MH, Ellard, S, Klimes, I, Szopa, M, Polak, M, Iafusco, D, Hattersley, AT, Njolstad, PR, Houghton, J, Patel, KA, Mathews, F, De Franco, E, Ford, T, Pillai, JK, Finn, R, Chakera, A, Iotova, V, Malecki, MT, Klupa, T, Gasperikova, D, Stanik, J, Barak, L, Dankovcikova, A, Palko, M, Walker, J, Visser, U, Howard, N, Lafferty, T, Cummings, E, Guntamukkala, P, Rose, D, Hughes, N, Couch, B, Punthakee, Z, Van der Meulen, J, LeGault, L, Sanderson, S, Krishnaswamy, R, Ho, J, Modgil, G, Lambert, P, Shield, JPH, Hoddinott, R, Burrows, A, Chetan, R, Hakeem, V, Werner, A, Muther, S, Deiss, D, Raile, K, Weisner, T, Kapellen, T, Akkurt, I, Menzel, U, Klinge, A, Schmidt, D, Heffernan, E, Carson, D, Uehara, A, Hasegawa, S, Kuulasmaa, H, Tuomi, T, Vermeulen, G, Mul, D, Jaap, A, Hill, D, Hunter, I, Rincon, M, McVie, R, Williams, T, Saxena, V, Al-Abdullah, A, Tinklin, T, Kaufman, E, Davis, L, O'Riordan, S, O'Connell, SM, Holl, R, Schebek, M, De Gallen, B, Voorhoeve, P, Malievsky, O, Mathew, R, Abdul-Latif, H, Aisenberg, J, Ioacara, S, Cameron, FJ, Sanchez, J, Jones, K, Van der Velde, R, Van den Bergh, J, Woodhead, H, Tjora, E, Irgens, H, Hogåsen, AK, Odegard, R, Hathout, EH, Nuboer, R, Pruhova, S, Shehadeh, N, Silva, JMCL, Cave, H, Fauret, A-L, Hoarau, M, Coutant, R, Metz, C, Bertrand, A-M, Bruel, H, Cartigny, M, Weill, J, Bizzarri, C, Bonfanti, R, Cadario, F, Cauvin, V, Chiari, G, Delvecchio, M, Piccinno, E, Faleschini, E, Pesavento, R, Rabbone, I, and Tumini, S

Abstract

BACKGROUND: KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. METHODS: In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817. FINDINGS: 90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3-10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA1c and sulfonylurea at al

Published
2018

29. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C, Burmeister, T, Groger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, NC, Emerenciano, M, Pombo-de-Oliveira, MS, Blunck, CB, Lopes, BA, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Abascal, LC, van der Velden, Vincent, Delabesse, E, Park, TS, Oh, SH, Silva, MLM, Lund-Aho, T, Juvonen, V, Moore, AS, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, zur Stadt, U, Lentes, J, Gohring, G, Kustanovich, A, Aleinikova, O, Schafer, BW, Kubetzko, S, Madsen, HO, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, JM, Clappier, E, Alonso, CN (Cristina), Zwaan, C.M., Van den Heuvel - Eibrink, Marry, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Moricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, OA, Panzer-Grumayer, R, Sedek, L, Szczepanski, T, Caye, A, Suarez, L, Cave, H, Marschalek, R, Meyer, C, Burmeister, T, Groger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, NC, Emerenciano, M, Pombo-de-Oliveira, MS, Blunck, CB, Lopes, BA, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Abascal, LC, van der Velden, Vincent, Delabesse, E, Park, TS, Oh, SH, Silva, MLM, Lund-Aho, T, Juvonen, V, Moore, AS, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, zur Stadt, U, Lentes, J, Gohring, G, Kustanovich, A, Aleinikova, O, Schafer, BW, Kubetzko, S, Madsen, HO, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, JM, Clappier, E, Alonso, CN (Cristina), Zwaan, C.M., Van den Heuvel - Eibrink, Marry, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Moricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, OA, Panzer-Grumayer, R, Sedek, L, Szczepanski, T, Caye, A, Suarez, L, Cave, H, and Marschalek, R

Published
2018

32. Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome

Author

Pannone, L, Bocchinfuso, G, Flex, E, Rossi, C, Baldassarre, G, Lissewski, C, Pantaleoni, F, Consoli, F, Lepri, F, Magliozzi, M, Anselmi, M, Delle Vigne, S, Sorge, G, Karaer, K, Cuturilo, G, Sartorio, A, Tinschert, S, Accadia, M, Digilio, M, Zampino, G, De Luca, A, Cave, H, Zenker, M, Gelb, B, Dallapiccola, B, Stella, L, Ferrero, G, Martinelli, S, and Tartaglia, M

Subjects
Models, Molecular, PTPN11 mutations, MAP Kinase Signaling System, Noonan syndrome, genotype-phenotype correlation analysis, structural and functional studies, Mutation, Missense, Protein Tyrosine Phosphatase, Non-Receptor Type 11, src Homology Domains, HEK293 Cells, Protein Domains, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Mutation, Genetics, Humans, Genetics (clinical), Genetic Predisposition to Disease, Settore CHIM/02 - Chimica Fisica, Protein Binding
Abstract

Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu

Published
2017

34. Genotype and phenotype spectrum of NRAS germline variants

Author

Altmuller, F., Lissewski, C., Bertola, D., Flex, E., Stark, Z., Spranger, S., Baynam, G., Buscarilli, M., Dyack, S., Gillis, J., Yntema, H.G., Pantaleoni, F., Loon, R.L. van, MacKay, S., Mina, K., Schanze, I., Tan, T.Y., Walsh, M., White, S.M., Niewisch, M.R., Garcia-Minaur, S., Plaza, D., Ahmadian, M.R., Cave, H., Tartaglia, M., Zenker, M., Altmuller, F., Lissewski, C., Bertola, D., Flex, E., Stark, Z., Spranger, S., Baynam, G., Buscarilli, M., Dyack, S., Gillis, J., Yntema, H.G., Pantaleoni, F., Loon, R.L. van, MacKay, S., Mina, K., Schanze, I., Tan, T.Y., Walsh, M., White, S.M., Niewisch, M.R., Garcia-Minaur, S., Plaza, D., Ahmadian, M.R., Cave, H., Tartaglia, M., and Zenker, M.

Abstract

Item does not contain fulltext, RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c.35G>A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c.34G>C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.

Published
2017

35. PREDICTIVE VALUE OF IG/TR AND BCR/ABL1 PCR-BASED MINIMAL RESIDUAL DISEASE MONITORING IN PH plus PEDIATRIC ALL TREATED WITH IMATINIB IN THE ESPHALL STUDY

Author

Cazzaniga, G., Lorenzo, P., Alten, J., Roettgers, S., Hancock, J., Saha, V., Castor, A., Madsen, H., Gandemer, V., Cave, H., Leoni, V., Ferrari, G., Pieters, R., Velden, V., Stary, J., Zuna, J., Escherich, G., Zur Stadt, U., Maurizio Arico', Conter, V., Schrappe, M., Valsecchi, M. G., Biondi, A., Centre Hospitalier Universitaire [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, education, [SDV.GEN] Life Sciences [q-bio]/Genetics, social sciences, humanities, geographic locations, health care economics and organizations
Abstract

International audience; 21st Congress of the European-Hematology-Association

Published
2016

38. Ikzf1 Deletion Status Discriminates For Outcome In Imatinibtreated Bcr-Abl1-Positive Childhood ALL

Author

Veer, A, Zaliova, M, Mottadelli, F, Lorenzo, P, Kronnie, G, Harrison, C, Cave, H, Trka, J, Saha, V, Schrappe, M, Pieters, R, BIONDI, ANDREA, VALSECCHI, MARIA GRAZIA, Stanulla, M, Boer, M, Cazzaniga, G., Veer, A, Zaliova, M, Mottadelli, F, Lorenzo, P, Kronnie, G, Harrison, C, Cave, H, Trka, J, Saha, V, Schrappe, M, Pieters, R, Biondi, A, Valsecchi, M, Stanulla, M, Boer, M, and Cazzaniga, G

Subjects
Bcr-Abl1-Positive, Acute Lymphoblastic Leukemia, Childhood, Ikzf1
Published
2013

39. Transient Neonatal Diabetes: the 6q24 phenotype

Author

Temple, I.K., Mackay, D.J.G., Coupe, A.-M., Cave, H., Polak, M., Siebert, R., Barber, J.C.K., Robinson, D.O., and Shield, J.P.H.

Subjects
Human genetics -- Research, Diabetes -- Genetic aspects, Genetic disorders -- Research, Biological sciences
Published
2001

41. An intragenic ERG deletion (ERGdel) is a marker of an oncogenic subtype of B-cell precursor acute lymphoblastic leukemia with a favorable outcome despite frequent IKZF1 deletions

Author

Emmanuelle Clappier, Marie-Françoise Auclerc, Jerome Rapion, Marleen Bakkus, Aurélie Caye, Ahlène Khemiri, Christine Giroux, Lucie Hernandez, Emmanuelle Kabongo, Suvi Savola, Thierry Leblanc, Karima Yakouben, Geneviève Plat, Costa, V., Ferster, A., Girard, S., Odile Fenneteau, Jean-Michel Cayuela, François Sigaux, Nicole Dastugue, Suciu, S., Benoit, Y., Yves Bertrand, Jean Soulier, Cave, H., and Hematology

Subjects
B-cell precursor acute lymphoblastic leukemia, ERG, Molecular diagnostics, IKZF1
Abstract

Oncogenic subtypes in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are used for risk-stratification. However, a significant number of BCPALLpatients are still genetically unassigned. Using array-CGH in a selected BCPALL cohort, we characterized a recurrent V(D)J-mediated intragenic deletion of the ERG gene (ERGdel). A breakpoint-specific PCR assay was designed and used to screen an independent non-selected cohort of 897 children aged 1-17 years treated for BCP-ALL in the EORTC-CLG 58951 trial. ERGdel was found in 29/897 patients (3.2%) and was mutually exclusive of known classifying genetic lesions, suggesting that it characterized a distinct leukemia entity. ERGdel was associated with higher age (median 7.0 years vs. 4.0 years, P=0.004), aberrant CD2 expression (43.5% vs. 3.7%, P

Published
2014

42. Standardization and quality control studies of 'real time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - A Europe Against Cancer Program

Author

Gabert, J, Beillard, E, van der Velden, V, Bi, W, Grimwade, D, Pallisgaard, N, Barbany, G, Cazzaniga, G, Cayuela, J, Cave, H, Pane, F, Aerts, J, De Micheli, D, Thirion, X, Pradel, V, Gonzalez, M, Viehmann, S, Malec, M, Saglio, G, van Dongen, J, Gabert J., Beillard E., van der Velden V. H. J., Bi W., Grimwade D., Pallisgaard N., Barbany G., Cazzaniga G., Cayuela J. M., Cave H., Pane F., Aerts J. L. E., De Micheli D., Thirion X., Pradel V., Gonzalez M., Viehmann S., Malec M., Saglio G., van Dongen J. J. M., Gabert, J, Beillard, E, van der Velden, V, Bi, W, Grimwade, D, Pallisgaard, N, Barbany, G, Cazzaniga, G, Cayuela, J, Cave, H, Pane, F, Aerts, J, De Micheli, D, Thirion, X, Pradel, V, Gonzalez, M, Viehmann, S, Malec, M, Saglio, G, van Dongen, J, Gabert J., Beillard E., van der Velden V. H. J., Bi W., Grimwade D., Pallisgaard N., Barbany G., Cazzaniga G., Cayuela J. M., Cave H., Pane F., Aerts J. L. E., De Micheli D., Thirion X., Pradel V., Gonzalez M., Viehmann S., Malec M., Saglio G., and van Dongen J. J. M.

Abstract

Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytc leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeliod leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer (EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n=278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multi-center therapeutic trials.

Published
2003

46. LIN28B is over-expressed in specific subtypes of pediatric leukemia and regulates lncRNA H19

Author

Helsmoortel, H. H., primary, De Moerloose, B., additional, Pieters, T., additional, Ghazavi, F., additional, Bresolin, S., additional, Cave, H., additional, de Vries, A., additional, de Haas, V., additional, Flotho, C., additional, Labarque, V., additional, Niemeyer, C., additional, De Paepe, P., additional, Van Roy, N., additional, Stary, J., additional, van den Heuvel-Eibrink, M. M., additional, Benoit, Y., additional, Schulte, J., additional, Goossens, S., additional, Berx, G., additional, Haigh, J. J., additional, Speleman, F., additional, Van Vlierberghe, P., additional, and Lammens, T., additional

Published
2016
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48. Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome

Author

Cordeddu, V., Yin, J. C., Gunnarsson, C., Virtanen, C., Drunat, S., Lepri, F., De Luca, A., Rossi, C., Ciolfi, A., Pugh, T. J., Bruselles, A., Priest, J. R., Pennacchio, L. A., Lu, Z., Danesh, A., Quevedo, R., Hamid, A., Martinelli, S., Pantaleoni, F., Gnazzo, M., Daniele, P., Lissewski, C., Bocchinfuso, G., Stella, L., Odent, S., Philip, N., Faivre, L., Vlckova, M., Seemanova, E., Digilio, C., Zenker, M., Zampino, Giuseppe, Verloes, A., Dallapiccola, B., Roberts, A. E., Cave, H., Gelb, B. D., Neel, B. G., Tartaglia, M., Zampino G. (ORCID:0000-0003-3865-3253), Cordeddu, V., Yin, J. C., Gunnarsson, C., Virtanen, C., Drunat, S., Lepri, F., De Luca, A., Rossi, C., Ciolfi, A., Pugh, T. J., Bruselles, A., Priest, J. R., Pennacchio, L. A., Lu, Z., Danesh, A., Quevedo, R., Hamid, A., Martinelli, S., Pantaleoni, F., Gnazzo, M., Daniele, P., Lissewski, C., Bocchinfuso, G., Stella, L., Odent, S., Philip, N., Faivre, L., Vlckova, M., Seemanova, E., Digilio, C., Zenker, M., Zampino, Giuseppe, Verloes, A., Dallapiccola, B., Roberts, A. E., Cave, H., Gelb, B. D., Neel, B. G., Tartaglia, M., and Zampino G. (ORCID:0000-0003-3865-3253)

Abstract

The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering Son of Sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology (DH) domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its autoinhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the DH domain.

Published
2015

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