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RNAseq dataset for MALT1 in MCL

Manuscript Title: Co-targeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma Journal: Journal of Clinical Investigation Authors Vivian Changying Jiang1, Yang Liu1, Junwei Lian1, Shengjian Huang1, Alexa Jordan1, Qingsong Cai1, Fangfang Yan3, Joseph Mitchell McIntosh1, Yijing Li1, Yuxuan Che1, Zhihong Chen1, Jovanny Vargas1, Maria Badillo1, JohnNelson Bigcal1, Heng-Huan Lee1, Wei Wang1, Yixin Yao1, Lei Nie1, Christopher Flowers1, and Michael Wang1, 2* Abstract Bruton’s tyrosine kinase (BTK) is a proven target in mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma. However, resistance to BTK inhibitors is a major clinical challenge. We here report that MALT1 is one of the top overexpressed genes in ibrutinib-resistant MCL cells, while expression of CARD11, which is upstream of MALT1, is decreased. MALT1 genetic knockout or inhibition produced dramatic defects in MCL cell growth regardless of ibrutinib sensitivity. Conversely, CARD11 knockout cells showed anti-tumor effects only in ibrutinib-sensitive cells, suggesting that MALT1 overexpression could drive ibrutinib resistance via bypassing BTK-CARD11 signaling. Additionally, BTK knockdown and MALT1 knockout markedly impaired MCL tumor migration and dissemination, and MALT1 pharmacological inhibition decreased MCL cell viability, adhesion, and migration by suppressing NF-κB, PI3K-ATK-mTOR, and integrin signaling. Importantly, co-targeting MALT1 with safimaltib and BTK with pirtobrutinib induced potent anti-MCL activity in ibrutinib-resistant MCL cell lines and patient-derived xenografts. Therefore, we conclude that MALT1 overexpression associates with resistance to BTK inhibitors in MCL, targeting abnormal MALT1 activity could be a promising therapeutic strategy to overcome BTK inhibitor resistance, and co-targeting of MALT1 and BTK should improve MCL treatment efficacy and durability as well as patient outcomes. Dataset description: The bulk RNA-seq dataset was generated for the cell lines below and used for two major purposes: 1. DEG analysis and GSEA analysis comparing IBN-R and IBN-S cells 2. DEG analysis and GSEA analysis comparing MCL cells with/without MI-2 treatment. sample Cell MI-2 Ibrutinib (IBN) Venetoclax (VEN) Used for IBN-R vs IBN-S comparison Used for MI-2 vs untreated (DMSO) H9 Granta519 - R S yes H21 Granta519 - R S yes H33 Granta519 - R S yes H10 Granta519-VEN-R - R R yes H22 Granta519-VEN-R - R R yes H34 Granta519-VEN-R - R R yes H3 JeKo BTK KD_1 - R R yes yes H15 JeKo BTK KD_1 - R R yes yes H27 JeKo BTK KD_1 - R R yes yes H5 JeKo BTK KD_2 - R R yes yes H17 JeKo BTK KD_2 - R R yes yes H29 JeKo BTK KD_2 - R R yes yes H1 JeKo-1 - S R yes yes H13 JeKo-1 - S R yes yes H25 JeKo-1 - S R yes yes H7 Mino - S S yes H19 Mino - S S yes H31 Mino - S S yes H8 Mino-VEN-R - S R yes H20 Mino-VEN-R - S R yes H32 Mino-VEN-R - S R yes H11 Rec-1 - S S yes H23 Rec-1 - S S yes H12 Rec-VEN-R - S S yes H24 Rec-VEN-R - S R yes H36 Rec-VEN-R - S R yes H35 Rec-1 -- S R yes H4 JeKo BTK KD_1 + MI-2 + yes H16 JeKo BTK KD_1 + MI-2 + yes H28 JeKo BTK KD_1 + MI-2 + yes H6 JeKo BTK KD_2 + MI-2 + yes H18 JeKo BTK KD_2 + MI-2 + yes H30 JeKo BTK KD_2 + MI-2 + yes H2 JeKo-1 + MI-2 + yes H14 JeKo-1 + MI-2 + yes H26 JeKo-1 + MI-2 + yes

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the data access policy for MALT1 in Mantle Cell Lymphoma

DATA ACCESS AGREEMENT These terms and conditions govern access to the managed access datasets (details of which are set out in Appendix I) to which the User Institution has requested access. The User Institution agrees to be bound by these terms and conditions. Definitions Authorized Personnel: The individuals at the User Institution to whom Dr. Michael Wang grants access to the Data. This includes the User, the individuals listed in Appendix II and any other individuals for whom the User Institution subsequently requests access to the Data. Details of the initial Authorized Personnel are set out in Appendix II. Data: The managed access datasets to which the User Institution has requested access. Data Producers: Dr. Michael Wang and the collaborators listed in Appendix I responsible for the development, organization, and oversight of these Data. External Collaborator: A collaborator of the User, working for an institution other than the User Institution. Project: The project for which the User Institution has requested access to these Data. A description of the Project is set out in Appendix II. Publications: Includes, without limitation, articles¬¬¬ published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research. Research Participant: An individual whose data form part of these Data. Research Purposes: Shall mean research that is seeking to advance the understanding of genetics and genomics, including the treatment of disorders, and work on statistical methods that may be applied to such research. User: The principal investigator for the Project. User Institution(s): The Institution that has requested access to the Data. XXXXX: Your Institution details here 1. The User Institution agrees to only use these Data for the purpose of the Project (described in Appendix II) and only for Research Purposes. The User Institution further agrees that it will only use these Data for Research Purposes which are within the limitations (if any) set out in Appendix I. 2. The User Institution agrees to preserve, at all times, the confidentiality of these Data. In particular, it undertakes not to use, or attempt to use these Data to compromise or otherwise infringe the confidentiality of information on Research Participants. Without prejudice to the generality of the foregoing, the User Institution agrees to use at least the measures set out in Appendix I to protect these Data. 3. The User Institution agrees to protect the confidentiality of Research Participants in any research papers or publications that they prepare by taking all reasonable care to limit the possibility of identification. 4. The User Institution agrees not to link or combine these Data to other information or archived data available in a way that could re-identify the Research Participants, even if access to that data has been formally granted to the User Institution or is freely available without restriction. 5. The User Institution agrees only to transfer or disclose these Data, in whole or part, or any material derived from these Data, to the Authorized Personnel. Should the User Institution wish to share these Data with an External Collaborator, the External Collaborator must complete a separate application for access to these Data. 6. The User Institution agrees that the Data Producers, and all other parties involved in the creation, funding or protection of these Data: a) make no warranty or representation, express or implied as to the accuracy, quality or comprehensiveness of these Data; b) exclude to the fullest extent permitted by law all liability for actions, claims, proceedings, demands, losses (including but not limited to loss of profit), costs, awards damages and payments made by the Recipient that may arise (whether directly or indirectly) in any way whatsoever from the Recipient’s use of these Data or from the unavailability of, or break in access to, these Data for whatever reason and; c) bear no responsibility for the further analysis or interpretation of these Data. 7. The User Institution agrees to follow the Fort Lauderdale Guidelines (http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document/wtd003207.pdf ) and the Toronto Statement (http://www.nature.com/nature/journal/v461/n7261/full/461168a.html). This includes but is not limited to recognizing the contribution of the Data Producers and including a proper acknowledgement in all reports or publications resulting from the use of these Data. 8. The User Institution agrees to follow the Publication Policy in Appendix III. This includes respecting the moratorium period for the Data Producers to publish the first peer-reviewed report describing and analyzing these Data. 9. The User Institution agrees not to make intellectual property claims on these Data and not to use intellectual property protection in ways that would prevent or block access to, or use of, any element of these Data, or conclusion drawn directly from these Data. 10. The User Institution can elect to perform further research that would add intellectual and resource capital to these data and decide to obtain intellectual property rights on these downstream discoveries. In this case, the User Institution agrees to implement licensing policies that will not obstruct further research and to follow the U.S. National Institutes of Health Best Practices for the Licensing of Genomic Inventions (2005) (https://www.icgc.org/files/daco/NIH_BestPracticesLicensingGenomicInventions_2005_en.pdf ) in conformity with the Organization for Economic Co-operation and Development Guidelines for the Licensing of the Genetic Inventions (2006) (http://www.oecd.org/science/biotech/36198812.pdf ). 11. The User Institution agrees to destroy/discard the Data held, once it is no longer used for the Project, unless obliged to retain the data for archival purposes in conformity with audit or legal requirements. 12. The User Institution will notify Dr. Michael Wang within 30 days of any changes or departures of Authorized Personnel. 13. The User Institution will notify Dr. Michael Wang prior to any significant changes to the protocol for the Project. 14. The User Institution will notify Dr. Michael Wang as soon as it becomes aware of a breach of the terms or conditions of this agreement. 15. Dr. Michael Wang may terminate this agreement by written notice to the User Institution. If this agreement terminates for any reason, the User Institution will be required to destroy any Data held, including copies and backup copies. This clause does not prevent the User Institution from retaining these data for archival purpose in conformity with audit or legal requirements. 16. The User Institution accepts that it may be necessary for the Data Producers to alter the terms of this agreement from time to time. As an example, this may include specific provisions relating to the Data required by Data Producers other than Dr. Michael Wang. In the event that changes are required, the Data Producers or their appointed agent will contact the User Institution to inform it of the changes and the User Institution may elect to accept the changes or terminate the agreement. 17. If requested, the User Institution will allow data security and management documentation to be inspected to verify that it is complying with the terms of this agreement. 18. The User Institution agrees to distribute a copy of these terms to the Authorized Personnel. The User Institution will procure that the Authorized Personnel comply with the terms of this agreement. 19. This agreement (and any dispute, controversy, proceedings or claim of whatever nature arising out of this agreement or its formation) shall be construed, interpreted and governed by the laws of England and Wales and shall be subject to the exclusive jurisdiction of the English courts.

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001006832 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00007809139 bam 1.8 GB
EGAF00007809140 bam 1.4 GB
EGAF00007809141 bam 1.3 GB
EGAF00007809142 bam 1.4 GB
EGAF00007809143 bam 1.7 GB
EGAF00007809144 bam 1.4 GB
EGAF00007809145 bam 1.6 GB
EGAF00007809146 bam 1.3 GB
EGAF00007809147 bam 1.7 GB
EGAF00007809148 bam 1.3 GB
EGAF00007809149 bam 1.5 GB
EGAF00007809150 bam 844.2 MB
EGAF00007809151 bam 1.5 GB
EGAF00007809152 bam 1.3 GB
EGAF00007809153 bam 1.3 GB
EGAF00007809154 bam 1.1 GB
EGAF00007809155 bam 1.4 GB
EGAF00007809156 bam 1.4 GB
EGAF00007809157 bam 1.6 GB
EGAF00007809158 bam 1.6 GB
EGAF00007809159 bam 1.1 GB
EGAF00007809160 bam 1.5 GB
EGAF00007809161 bam 1.4 GB
EGAF00007809162 bam 1.2 GB
EGAF00007809163 bam 1.3 GB
EGAF00007809164 bam 1.3 GB
EGAF00007809165 bam 1.1 GB
EGAF00007809166 bam 1.5 GB
EGAF00007809167 bam 1.4 GB
EGAF00007809168 bam 1.9 GB
EGAF00007809169 bam 1.5 GB
EGAF00007809170 bam 1.7 GB
EGAF00007809171 bam 1.3 GB
EGAF00007809172 bam 1.4 GB
EGAF00007809173 bam 1.4 GB
EGAF00007809174 bai 4.0 MB
EGAF00007809175 bai 3.9 MB
EGAF00007809176 bai 3.7 MB
EGAF00007809177 bai 4.3 MB
EGAF00007809178 bai 4.0 MB
EGAF00007809179 bai 4.1 MB
EGAF00007809180 bai 4.0 MB
EGAF00007809181 bai 3.9 MB
EGAF00007809182 bai 3.6 MB
EGAF00007809183 bai 4.0 MB
EGAF00007809184 bai 3.8 MB
EGAF00007809185 bai 4.1 MB
EGAF00007809186 bai 4.0 MB
EGAF00007809187 bai 3.7 MB
EGAF00007809188 bai 3.9 MB
EGAF00007809189 bai 4.1 MB
EGAF00007809190 bai 4.2 MB
EGAF00007809191 bai 4.0 MB
EGAF00007809192 bai 4.1 MB
EGAF00007809193 bai 3.9 MB
EGAF00007809194 bai 4.0 MB
EGAF00007809195 bai 3.9 MB
EGAF00007809196 bai 4.0 MB
EGAF00007809197 bai 3.9 MB
EGAF00007809198 bai 4.2 MB
EGAF00007809199 bai 3.5 MB
EGAF00007809200 bai 4.0 MB
EGAF00007809201 bai 4.0 MB
EGAF00007809202 bai 4.3 MB
EGAF00007809203 bai 4.2 MB
EGAF00007809204 bai 4.0 MB
EGAF00007809205 bai 4.0 MB
EGAF00007809206 bai 3.8 MB
EGAF00007809207 bai 3.8 MB
69 Files (49.6 GB)