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3. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma

Author

Muppidi, Jagan R., Schmitz, Roland, Green, Jesse A., Xiao, Wenming, Larsen, Adrien B., Braun, Sterling E., An, Jinping, Xu, Ying, Rosenwald, Andreas, Ott, German, Gascoyne, Randy D., Rimsza, Lisa M., Campo, Elias, Jaffe, Elaine S., Delabie, Jan, Smeland, Erlend B., Braziel, Rita M., Tubbs, Raymond R., Cook, J. R., Weisenburger, Dennis D., Chan, Wing C., Vaidehi, Nagarajan, Staudt, Louis M., and Cyster, Jason G.

Subjects
Genetic research, Lymphomas -- Genetic aspects, B cells -- Physiological aspects, Cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined (1,2). Work in mice showed that sphingosine-l-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells (3,4). Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5-7). Here we show, using in vitro and in vivo assays, that GCBDLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma., We sequenced the S1PR2 coding region in 117 GCB-DLBCL, 31 Burkitt's lymphoma and 68 activated B-cell-like (ABC)-DLBCL samples. Twelve S1PR2 coding mutations were identified in the GCB-DLBCL samples versus one [...]

Published
2014

14. CHARACTERIZATION OF THE GENETIC LANDSCAPE OF HIGH‐GRADE B‐CELL LYMPHOMA, NOS – AN LLMPP PROJECT

Author

Collinge, B. J., primary, Hilton, L. K, additional, Wong, J., additional, Ben‐Neriah, S., additional, Rushton, C. K., additional, Slack, G. W., additional, Farinha, P., additional, Cook, J. R., additional, Ott, G., additional, Rosenwald, A., additional, Campo, E., additional, Amador, C., additional, Greiner, T. C., additional, Raess, P. W., additional, Song, J. Y., additional, Inghirami, G., additional, Jaffe, E. S., additional, Weisenburger, D. D., additional, Chan, W. C., additional, Holte, H., additional, Beiske, K., additional, Fu, K., additional, Delabie, J., additional, Pittaluga, S., additional, Feldman, A. L., additional, Savage, K. J., additional, Mungall, A. J., additional, Staudt, L. M., additional, Steidl, C., additional, Rimsza, L. M., additional, Morin, R. D., additional, and Scott, D. W., additional

Published
2021
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15. THE MUTATIONAL LANDSCAPE OF DOUBLE/TRIPLE‐HIT HIGH‐GRADE B‐CELL LYMPHOMA WITH BCL2 REARRANGEMENT (DH/TH‐ BCL2 ) – AN LLMPP PROJECT

Author

Collinge, B. J., primary, Hilton, L. K., additional, Wong, J., additional, Ben‐Neriah, S., additional, Alduaij, W., additional, Rushton, C. K., additional, Slack, G. W., additional, Farinha, P., additional, Miyata‐Takata, T., additional, Cook, J. R., additional, Ott, G., additional, Rosenwald, A., additional, Campo, E., additional, Amador, C., additional, Greiner, T. C., additional, Raess, P. W., additional, Song, J. Y., additional, Inghirami, G., additional, Jaffe, E. S., additional, Weisenburger, D. D., additional, Chan, W. C., additional, Holte, H., additional, Beiske, K., additional, Fu, K., additional, Delabie, J., additional, Pittaluga, S., additional, Feldman, A. L., additional, Sehn, L. H., additional, Savage, K. J., additional, Mungall, A. J., additional, Staudt, L. M., additional, Steidl, C., additional, Rimsza, L. M., additional, Morin, R. D., additional, and Scott, D. W., additional

Published
2021
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16. THE TOPOLOGY OF MYC REARRANGEMENTS IN DOUBLE‐HIT LYMPHOMA IS CONSTRAINED BY THE PRECEDING IGH‐BCL2 REARRANGEMENT – AN LLMPP PROJECT

Author

Hilton, L. K., primary, Collinge, B., additional, Ben‐Neriah, S., additional, Grande, B. M., additional, Slack, G. W., additional, Farinha, P., additional, Miyata‐Takata, T., additional, Cook, J. R., additional, Ott, G., additional, Rosenwald, A., additional, Campo, E., additional, Amador, C., additional, Greiner, T. C., additional, Raess, P. W., additional, Song, J. Y., additional, Inghirami, G., additional, Jaffe, E. S., additional, Weisenburger, D. D., additional, Chan, W. C., additional, Holte, H., additional, Beiske, K., additional, Fu, K., additional, Delabie, J., additional, Pittaluga, S., additional, Feldman, A. L., additional, Sehn, L. H., additional, Savage, K. J., additional, Mungall, A. J., additional, Staudt, L. M., additional, Steidl, C., additional, Rimsza, L. M., additional, Morin, R. D., additional, and Scott, D. W., additional

Published
2021
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22. Oncogenically active MYD88 mutations in human lymphoma

Author

Ngo, Vu N., Young, Ryan M., Schmitz, Roland, Jhavar, Sameer, Xiao, Wenming, Lim, Kian-Huat, Kohlhammer, Holger, Xu, Weihong, Yang, Yandan, Zhao, Hong, Shaffer, Arthur L., Romesser, Paul, Wright, George, Powell, John, Rosenwald, Andreas, Muller-Hermelink, Hans Konrad, Ott, German, Gascoyne, Randy D., Connors, Joseph M., Rimsza, Lisa M., Campo, Elias, Jaffe, Elaine S., Delabie, Jan, Smeland, Erlend B., Fisher, Richard I., Braziel, Rita M., Tubbs, Raymond R., Cook, J. R., Weisenburger, Denny D., Chan, Wing C., and Staudt, Louis M.

Published
2011
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24. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma

Author

Davis, Eric R., Ngo, Vu N., Lenz, Georg, Tolar, Pavel, Young, Ryan M., Romesser, Paul B., Kohlhammer, Holger, Lamy, Laurence, Zhao, Hong, Yang, Yandan, Xu, Weihong, Shaffer, Arthur L., Wright, George, Xiao, Wenming, Powell, John, Jiang, Jian-kang, Thomas, Craig J., Rosenwald, Andreas, Ott, German, Muller-Hermelink, Hans Konrad, Gascoyne, Randy D., Connors, Joseph M., Johnson, Nathalie A., Rimsza, Lisa M., Campo, Elias, Jaffe, Elaine S., Wilson, Wyndham H., Delabie, Jan, Smeland, Erlend B., Fisher, Richard I., Braziel, Rita M., Tubbs, Raymond R., Cook, J. R., Weisenburger, Dennis D., Chan, Wing C., Pierce, Susan K., and Staudt, Louis M.

Published
2010
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27. Stromal Gene Signatures in Large-B-Cell Lymphomas

Author

Lenz, G., Wright, G., Dave, S. S., Xiao, W., Powell, J., Zhao, H., Xu, W., Tan, B., Goldschmidt, N., Iqbal, J., Vose, J., Bast, M., Fu, K., Weisenburger, D. D., Greiner, T. C., Armitage, J. O., Kyle, A., May, L., Gascoyne, R. D., Connors, J. M., Troen, G., Holte, H., Kvaloy, S., Dierickx, D., Verhoef, G., Delabie, J., Smeland, E. B., Jares, P., Martinez, A., Lopez-Guillermo, A., Montserrat, E., Campo, E., Braziel, R. M., Miller, T. P., Rimsza, L. M., Cook, J. R., Pohlman, B., Sweetenham, J., Tubbs, R. R., Fisher, R. I., Hartmann, E., Rosenwald, A., Ott, G., Muller-Hermelink, H. -K., Wrench, D., Lister, T. A., Jaffe, E. S., Wilson, W. H., Chan, W. C., and Staudt, L. M.

Published
2008
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28. Crew Launch Vehicle Upper Stage

Author

Davis, D. J and Cook, J. R

Subjects
Launch Vehicles And Launch Operations
Abstract

The Agency s Crew Launch Vehicle (CLV) will be the first human rated space transportation system developed in the United States since the Space Shuttle. The CLV will utilize existing Shuttle heritage hardware and systems combined with a "clean sheet design" for the Upper Stage. The Upper Stage element will be designed and developed by a team of NASA engineers managed by the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. The team will design the Upper Stage based on the Exploration Systems Architecture Study (ESAS) Team s point of departure conceptual design as illustrated in the figure below. This concept is a self-supporting cylindrical structure, approximately 1 15 feet long and 216 inches in diameter. While this "clean-sheet" upper stage design inherently carries more risk than utilizing a modified design, the approach also has many advantages. This paper will discuss the advantages and disadvantages of pursuing a "clean-sheet" design for the new CLV Upper Stage as well as describe in detail the overall design of the Upper Stage and its integration into NASA s CLV.

Published
2006

30. A Wavelength Optimization Study on Visible and Infrared Propagation Systems in Coastal Environments

Author

Reid, J. S, Tsay, Si-Chee, Moision, W. K, Gasso, S, Cook, J. R, Westphal, D. L, Paulus, R. A, Bucholtz, A, and Lau, William K. M

Subjects
Earth Resources And Remote Sensing
Abstract

Electro-optical (EO) systems employed for communications, surveillance and weapons systems are commonly assessed in the North American and European continents. However, the atmospheric propagation environment in these regions is often dissimilar to most other parts of the world. In particular, atmospheric dust, industrial pollution, and smoke frequently reduce visibility to less than 5 km in Asia and South America significantly hampering EO system performance. Because atmospheric aerosol species vary considerably in size and chemistry, optimal wavelengths for EO systems vary from region to region. In this paper we examine the extinction effects from aerosol particles and water vapor on a regional basis. Theoretical studies are coupled with visibility and satellite climatologies to make an assessment for the coastal regions of the world. While longer wavelengths permit higher transmission by particles in regions significantly hampered by fine mode particles (such as industrial pollution and smoke), this advantage is commonly offset by high extinction values from water vapor. This offsetting effect is particularly strong in industrial and developing countries in the tropics and sub-tropics such as Southeast Asia and South America. Conversely, the advantage of low water vapor concentrations in longer wavelengths is offset by high mass-extinction efficiencies of atmospheric dust in this portion of the spectrum.

Published
2002

32. Preliminary results of the NASA/industry hybrid propulsion program

Author

Goldberg, B. E and Cook, J. R

Subjects
Spacecraft Propulsion And Power
Abstract

NASA has been investigating the potential of hybrid propulsion, on and off, for the last thirty years. In 1989, a study to identify the required technologies for large boosters was funded and, in March of 1992, the NASA-Marshall formalized a coordinated program of research on hybrid propulsion. The cornerstone of this program is represented by a partnership between government and industry to test hybrid systems and technology in motors ranging up to 40,000 lbs thrust. New data indicate the presence of at least two different nonacoustic instability mechanisms.

Published
1992

44. UNITY Network Represents a New Generation of Native Youth.

Author

Cook, J. R.

Abstract

Describes the mission of the United National Indian Tribal Youth (UNITY) Network, which gives American Indian and Alaska Native youth, ages 15 to 24, a leadership role in personal, cultural, and national issues. Provides information on forming a Youth Council as part of the network. (HTH)

Published
1994

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