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ASH Summit on Immunotherapies for Hematologic Diseases

Call for Abstracts

Information for Authors

The American Society of Hematology (ASH) Summit on Immunotherapies for Hematologic Diseases will be held March 2-3, 2023 at the Omni Shoreham, Washington, DC. The goal of this meeting is to present the best new scientific research advances in immunotherapies and targeted therapies (i.e., gene editing and gene therapy) for hematologic diseases.

The ASH Summit on Immunotherapies for Hematologic Diseases Steering Committee:

  • encourages all interested individuals to attend the conference and to submit an abstract for poster and/or oral presentation; and
  • seeks original papers that address issues relating to immunotherapies and other targeted therapies (i.e., gene editing and gene therapy) in treating non-malignant and malignant hematologic disorders.

Abstracts submitted to this meeting are eligible for submission to the 2023 ASH Annual Meeting.

All abstract submissions must be made electronically through ASH’s online abstract submission system. The site opens on November 15, and the abstract submission deadline is Thursday, January 5, 2023 at 11:59 p.m. Pacific time.

Eligibility

To submit an abstract, research and/or studies must fit into one of the ASH Summit on Immunotherapies for Hematologic Diseases Abstract Review Categories.

Any of the following criteria will make an abstract ineligible for presentation at the ASH Summit on Immunotherapies for Hematologic Diseases:

  • Data are publicly available via major search engines (such as PubMed, Google Scholar, etc.).
  • Data are accepted for publication before the abstract submission closing date.
  • Data have been or are to be presented at a meeting of 1,000 or more participants before the ASH Summit on Immunotherapies for Hematologic Diseases.*

* Updated analyses will be considered only if the abstract is a significant extension of previously published work. The author must provide an explanation (see section below) to show how the abstract contains significant new information.

* Abstracts accepted for presentation or publication for the ASH 2022 Annual Meeting are exempted from the above restrictions.

Note: Abstracts submitted to the ASH 2023 Summit on Immunotherapies for Hematologic Diseases are eligible to be re-submitted to the 2023 ASH Annual Meeting.

Responsibilities of the Presenting Author

  • The first author listed for each abstract serves as the presenting author and as the primary contact for all correspondence regarding the abstract, unless otherwise specified under the “Authors” section of the online abstract submission system.
  • The presenting author must be one of the co-authors listed on the submitted abstract.
  • The presenting author is responsible for the following:
    • Ensuring that all authors have read the abstract and agreed to be co-authors. Failure to get approval from all authors will result in rejection of the abstract.
    • Notifying all co-authors of any additions, deletions, and changes to the program, as may be communicated by ASH.
    • Obtaining all of the conflict-of-interest disclosure and copyright transfer information from co-authors.
    • Forwarding all correspondence to all co-authors, including ASH policies and guidelines.

Authors’ Consent and Waiver of Claims

Each abstract author agrees and certifies that he or she:

  • has read all of the rules and agrees to be bound by them,
  • is responsible for submission of the abstract in accordance with the rules, and
  • waives any and all claims against ASH and any reviewer arising out of or relating to the abstract submission and review process, including but not limited to peer review and the grading of abstracts.

General Guidelines

  • The abstract must address scientific questions, detail clinical observations, or contain primary scientific data.
  • Abstracts submitted to this meeting are embargoed from the time of submission. This means that the data in the abstract cannot be presented at a meeting with 1,000 or more participants and/or published once submitted for the ASH Summit on Immunotherapies for Hematologic Diseases until the meeting is concluded. Read the “Embargo Policy” section of the Call for Abstracts for more information.
  • Authors assign copyright of the abstract to ASH upon submission (unless one of the authors is a U.S. Federal employee—in such case, ASH does not hold copyright) for use in the ASH Summit on Immunotherapies for Hematologic Diseases meeting materials. Authors retain copyright for all other uses after the meeting.
  • All research and studies reported in submitted abstracts that involve human and animal subjects must comply with the guiding principles for experimental procedures found in the Declaration of Helsinki of the World Medical Association.
  • Data from the long-term follow-up of previously presented clinical trials may be submitted only if significant new information can be shown. In this case, please use the Updated Analyses section of the abstract form to explain the significance of the new data. The reviewers will have this information available during their evaluation.
  • Interim analysis of a prospective randomized clinical trial will be considered only if it is performed as planned in the original protocol and is statistically valid. If your abstract involves interim analysis, use the Interim Analysis of a Clinical Trial section of the abstract form to explain the details of your study. The reviewers will have this information available during their evaluation.
  • There is a $60 nonrefundable handling fee for submitting an abstract. Payment must be made by credit card; Visa, MasterCard, and American Express are accepted. Purchase orders and checks will not be accepted. The abstract submission fee does not include registration for the ASH Summit on Immunotherapies for Hematologic Diseases; therefore, all authors planning to attend the ASH Summit on Immunotherapies for Hematologic Diseases must register for the meeting.
  • No revisions can be made after the abstract submission deadline.
  • Abstracts generally may not be withdrawn once submitted. If you prefer that your abstract be withdrawn for whatever reason, you must email a written request to [email protected].
  • The presentation at the meeting must reflect the submitted abstract. In particular, the abstract title, authorship, and scientific content of the presentation at the meeting must match the submitted abstract, although updates on results may be added.
  • Abstracts should be written in clear and concise English, so that reviewers are able to focus solely on the scientific merits of the submission. We encourage non-English-speaking authors to have their abstracts checked for grammar and spelling prior to submission.
  • It is assumed that the presenting author will have adequate command of English to present and to respond to questions.

Presentation Format

  • All abstracts submitted will be considered for poster presentation.
  • Abstracts deemed exceptional in original review will be passed on to the ASH Summit on Immunotherapies for Hematologic Diseases Steering Committee for further consideration for an oral presentation that would be part of an invited session.

All abstracts accepted for presentation will be published in the meeting app, available only to registered attendees. They will not be published or made available to the public in any form.

Abstract Review and Selection Process

  • After the submission deadline, all completed and eligible abstracts will be made available to the ASH Abstract Reviewers for blinded review and scoring, and final decisions will be made by the Steering Committee in late January 2023.
  • Abstracts will be evaluated and scored solely on their scientific merits.
  • Incomplete abstracts will not be reviewed.
  • The same study must not be submitted as multiple abstracts. Abstracts that are simply different versions of a single study will be rejected.
  • Abstracts will be peer reviewed according to the abstract categories. Authors must indicate during online submission the appropriate review category (one only). Please use the list of abstract review categories, which provides detailed descriptions of each category, to assist you in selecting the correct abstract classification. Read through all of the categories and select the category most closely associated with your abstract. All category selections will be final. There will be NO re-classification of abstracts after the abstract submission site has been closed. Abstracts submitted to the wrong category are scored in that category and usually fare poorly.
  • All abstracts submitted will be considered eligible for poster presentation. Poster Sessions allow the viewing of a poster illustration of the abstract. Authors are expected to post and remove posters at designated times and to be at their posters to answer questions during the time designated for poster presentations. The author’s attendance during poster presentation time will be monitored.
  • Abstracts deemed exceptional in original review will be passed on to the ASH Summit on Immunotherapies for Hematologic Diseases Steering Committee for further consideration for an oral presentation that would be part of an invited session.

Acceptance/Rejection Notification

  • Notification regarding acceptance or rejection of abstracts will be sent to the presenting author in late January 2023 by email; consequently, an accurate email address is critical. If you have not received an email notification by February 1, 2023, contact [email protected]. Rejection notifications will also be sent at that time.
  • To ensure that you are able to receive email correspondence from ASH, please make sure that your email software can receive mail from the confex.com and hematology.org domains. You should add [email protected] and [email protected] to your address book. If after completing your submission you don't receive a confirmation email from the abstract system, you must contact your system administrator and make sure that the hematology.org domain is added to your email address whitelist.
  • The decision of the ASH Summit on Immunotherapies for Hematologic Diseases Steering Committee regarding acceptance and presentation of abstracts is final.

Abstract Withdrawal

  • Once an abstract is accepted, a written request to withdraw must be submitted no later than February 1, 2023, to [email protected] if the first author decides to withdraw the abstract for any reason. Abstract withdrawal requests received after the deadline will be considered on a case-by-case basis.
  • ASH reserves the right to withdraw abstracts that are in violation of the Society’s policies and guidelines, such as those that have been previously published or presented (except at the most recent ASH annual meeting), have been deemed scientifically unsound, or have been found to include inaccurate data, etc.

Late-Breaking Abstracts

Recognizing that the results of timely top-quality research may not always be available by the general abstract submission deadline,
the ASH Summit on Immunotherapies for Hematologic Diseases Steering Committee
offers an option for late-breaking abstracts.

  • The late-breaking abstracts submission site will open January 24 and will close January 31, 2023.
  • During submission, authors of late-breaking abstracts will be asked to explain why their abstract was not ready by the regular deadline (January 5) and deserves to be considered as late-breaking. This information will be available to reviewers.
  • Only six abstracts will be accepted and will be presented in the Late-Breaking abstracts session. Authors should realize that selection for presentation is extremely competitive, with the quality and general significance of the presented Late-Breaking abstracts equivalent to Plenary Session or very top oral session abstracts.
  • There is a $60 nonrefundable handling fee for submitting a late-breaking abstract. Payment must be made by credit card; Visa, MasterCard, and American Express are accepted. Purchase orders and checks will not be accepted.
  • Late-breaking abstracts will undergo regular peer-review evaluation.
  • Work already posted to a preprint server will not be considered for the Late-Breaking Abstracts session.

Abstract Submission Policies

Conflict-of-Interest Disclosure Policy

  • ASH is committed to ensuring the integrity of its scientific, educational, and research programs. The ASH Conflict-of-Interest Policy requires disclosure of any financial or other interest in the biomedical industry that might be construed as resulting in an actual, potential, or apparent conflict, regardless of the relationship’s pertinence to the abstract, or abstracts if the author is associated with more than one abstract submitted to ASH.
  • ASH Policy requires that you disclose any financial relationship you or your spouse/partner have had within the past 24 months with an ineligible company (formerly commercial interest) as defined by the Accreditation Council for Continuing Medical Education (ACCME):
  • Ineligible companies are those whose primary business is producing, marketing, re-selling, or distributing healthcare products used by or on patients. Examples of such companies can be found on the ACCME website
  • For this purpose, “financial relationships” are those in which the individual benefits by receiving a salary, royalty, intellectual property rights, consulting fee, honoraria, ownership interest (e.g., stocks, stock options, or other ownership interest, excluding diversified mutual funds), or other financial benefit. Financial benefits are usually associated with roles such as employment, management position, independent contractor (including contracted research), consulting, speaking and teaching, membership on advisory committee or review panels, board memberships, and other activities from which remuneration is received, or expected. Research funding from ineligible companies should be disclosed by the principal or named investigator even if that individual’s institution receives the research grant and manages the funds.
  • By completing this section of the online abstract submission, you agree that you have read the ASH Conflict-of-Interest Policy and that you understand and support its intent.
  • This policy is not intended to prevent a presentation; it is merely intended to openly identify potential conflicts so that audience members may form their own judgments about the presentation with a full disclosure of the facts.

Author Responsibility Regarding Financial Relationship Disclosure

  • The presenting author is responsible for obtaining financial disclosure information from all co-authors.
  • All authors and co-authors are required to provide any information concerning personal or professional circumstances and financial relationships with ineligible companies that might reasonably be expected to affect the author’s view on the presentation.
  • This includes relationships with pharmaceutical companies, biomedical device manufacturers, biomedical startups that have begun a governmental regulatory approval process, or other companies whose products or services are related to the subject matter of the presentation topic. If no financial relationships with ineligible companies exist, this must be stated as well.

When to Disclose

Please disclose any relationships with ineligible companies regardless of the relationship’s pertinence to the content of the abstract, or abstracts if the author is associated with more than one abstract submitted to ASH. Disclosure includes relationships held by you or any individual with whom you directly share income.

What to Disclose

You must disclose the relationship type and the name of the ineligible company for each of the following areas in which you maintain a relationship. Exact dollar amounts are not necessary. You will have the option to (a) note that there are no financial relationships to disclose or to (b) provide relationship information. Disclosed information may include the following areas:

  • Employment (current or ended)
  • Consultancy
  • Current equity holder in publicly traded ineligible company
  • Current holder of individual stocks in a privately held ineligible company (excluding indirect investments through mutual funds and the like)
  • Current holder of stock options in a privately-held ineligible company;
  • Divested equity in a private or publicly-traded ineligible company in the past 24 months
  • Research funding (including grants received by your institution)
  • Honoraria directly received from an entity
  • Patents and royalties
  • Paid expert testimony
  • Membership on an entity’s board of directors, speaker’s bureau, or its advisory committees
  • Any other financial relationship with an ineligible company

Off-Label Use

You will be required to note whether your presentation will include discussion of off-label use of products. If so, please use the Off-Label Disclosure section of the abstract form to identify the product(s) and off-label use(s).

Other Areas

During the disclosure submission process, you will also be required to indicate your compliance with the following statements, which include measures to ensure clinical content validity:

  • Any recommendations for patient care must be based on current science, evidence, and clinical reasoning, while giving a fair and balanced view of diagnostic and therapeutic options.
  • All scientific research referred to, reported, or used in this educational activity in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, analysis, and interpretation.
  • If I discuss new and evolving topics for which there is a lower (or absent) evidence base, I will clearly identify it as such within the education and individual presentations.
  • The presentation of the information with which I am involved will avoid advocating for, or promoting, practices that are not, or not yet, adequately based on current science, evidence, and clinical reasoning.
  • The presentation of the information with which I am involved will exclude any advocacy for, or promotion of, unscientific approaches to diagnosis or therapy, or recommendations, treatment, or manners of practicing healthcare that are determined to have risks or dangers that outweigh the benefits or are known to be ineffective in the treatment of patients.
  • The content I am responsible for will only use generic names of products, or if trade names appear, is the use of those trade names will be justified (e.g., product is known more widely for the trade name or the product does not have a generic name).
  • The content I am responsible for will be free of logos or other corporate identifiers of healthcare industry companies, specifically those whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.
  • I will remove all patient identifiers (name, birth date, address, phone number, medical record number, account number, social security number, etc.) from my presentation materials. I will not use identifiable photographs of patients unless I have obtained written permission from the patient.
  • If I have been trained or utilized by an ineligible company (commercial interest) or its agent as a speaker (e.g. speakers’ bureau) for any commercial interest, the promotional aspects of that presentation will not be included in any way with this activity or publication.

ASH Statement on Commercial Interest Presenters

The primary purpose of this program is to advance the professional development of our learners in order to increase knowledge and improve the diagnosis and treatment of patients. In order to maintain the flow of the most current information to our attendees, the content may include information planned, presented, or authored by employees of commercial interests. ASH is committed to the integrity of the science presented at its activities and employs a rigorous peer review process to ensure that integrity. The content of presentations by commercial interest employees must focus on basic science and not on the product or on the commercial aspects of the discovery. In addition, the format of the presentation must permit full discussion of the therapeutic benefits and risks of the discovery.

How to Submit an Abstract

The abstract submission site is now open. All abstracts must be submitted by January 5, 2023, at 11:59 p.m., Pacific time. Submissions that are incomplete by the deadline will be rejected.

Submit an abstract

  • Abstracts must be submitted online through the official online abstract submission system. Email and word processing files not submitted through the site will not be accepted.
  • There is a $60 non-refundable handling fee for submitting an abstract. Payment must be made by credit card; Visa, MasterCard, and American Express are accepted. Purchase orders and checks will not be accepted. The abstract submission fee does not include registration for ASH Summit on Immunotherapies for Hematologic Diseases; therefore, all authors planning to attend the meeting must register for the meeting.
  • Once you have submitted the title page information, a draft of your abstract will be saved, and you will be able to return to edit and update it at any time until January 5, 2023, at 11:59 p.m., Pacific time. You will receive an email providing a link to your submission.
  • Abstracts cannot be submitted and will not be reviewed without proper payment and completion of the “Submission Information” and “Disclosure” sections of the online abstract submission program.
  • Any technical questions regarding the submission process should be directed to [email protected]

Preparing an Abstract for Submission

Contact Information

  • Your name, degree, institution, address, phone number, and email address must be provided. As the corresponding author, you will receive all future correspondence from ASH.
  • The corresponding author should be the first author (presenter) of the abstract, unless otherwise noted during submission.

Co-Authors

  • Names of co-authors and institutions must be provided. The program will automatically place an asterisk (*) after the name of each non-member author. Changes will not be made to the spelling of authors’ names after the submission deadline; please proof your co-authors’ names carefully.

Copyright Policy

  • Authors assign copyright of the abstract to ASH upon submission (unless one of the authors is a U.S. Federal employee—in such case, ASH does not hold copyright) for use in the ASH Summit on Immunotherapies for Hematologic Diseases meeting materials. Authors retain copyright for all other uses after the meeting.

Abstract Title

  • The abstract title should be brief and clearly indicate the nature of the abstract.
  • The abstract title must be in title case. Capitalize all nouns, pronouns, adjectives, verbs, adverbs, and subordinate conjunctions (i.e., as, because, although). Except for the first word of the title, lowercase all articles, coordinate conjunctions (i.e., and, or, nor), and prepositions, regardless of length. Also, lowercase “to” when used as an infinitive.
  • Additionally, keep letters lowercase if the lowercase letters have a specific meaning, such as pH or NaCl.
  • Do not put a period at the end of the title.
  • For example: Somatic Mutations in Schinzel-Giedion Syndrome Gene SETBP1 Determine Progression in Myeloid Malignancies

Use of Product Names

  • Non-proprietary (generic/scientific) names should be used and should be lowercase.
  • If necessary, you may include a proprietary name in parentheses directly following the generic name after its first mention in the body of the abstract; the first letter of the name of a proprietary drug should be capitalized. ASH reserves the right to replace proprietary names with generic names to adhere to this policy.

Abbreviations

Use standard abbreviations. Place abbreviations in parentheses immediately after the first mention of a term or phrase; the abbreviation can then be used throughout the abstract.

Abstract Body, Tables, and Figures

  • Abstracts will be typeset from the text submitted by the author without copyediting changes. It is the responsibility of the author to proofread the abstract carefully.
  • The entire body of the abstract, excluding tables, must not exceed 3,800 characters. Spaces are not included in this number. Title, authors’ names, affiliations, figures, and tables are not included in the character count.
  • The abstract may be structured (i.e., abstracts divided into sections using terms such as Introduction, Methods, Results, Conclusions, etc.) or unstructured.
  • Do not use bold type or underline formatting. Italic type is acceptable.
  • Text may be in multiple paragraphs.
  • Special Greek and mathematical symbols are available in a character map within the submission system.
  • Use numerals to indicate numbers, except when beginning sentences.
  • Any tables and figures that you wish to include must be uploaded as a single image. Do not paste a table directly into the text of the abstract, but rather include it as an image in the appropriate place and use the Upload method to submit your abstract. To convert a table to an image, we recommend taking a screenshot of the table. If using a PC, use the Snipping Tool or the Print Screen button. If using a Mac, press Command-Shift-4.
  • Any references should be noted as citations within the text and not as footnotes at the end.

Selection of Abstract Review Category

  • Please refer to the list of this year’s abstract review categories, which provides detailed descriptions of each category, to assist you in selecting the correct abstract classification.
  • Be sure to select from the review category that best describes your abstract. Note that the abstract will be reviewed in the category you selected; there is no re-classification once submission has closed.

Abstract Awards

ASH supports awards for high-scoring abstracts submitted by hematologists-in-training. All hematologists-in-training, who are both first-or-last author and presenter of the abstract, may request to be considered for an Abstract Achievement Award.

  • All hematologists-in-training, who are both first-or-last author and presenter of the abstract, are eligible for consideration for an Abstract Achievement Award. Submitters must first identify as a hematologist–in-training, select the appropriate training category (undergraduate student, medical student, graduate student, resident physician, or post-doctoral fellow), and opt into award consideration in the online abstract submission system.
  • As a hematologist-in-training, you are required to submit a letter from the senior investigator overseeing your research confirming your status as a hematologist-in-training.
  • Your letter must be typed on your institution’s letterhead, signed by the senior investigator, saved in PDF format, and uploaded to the online abstract submission system.
  • Please include the following items in your letter:
    • Author name (this is the hematologist-in-training who is the presenting/contact author)
    • Confirmation of your specific training category and status as a hematologist-in-training

All hematologist-in-training authors must upload the required letter into the program in order to complete the abstract submission. The deadline for receipt of the hematologist-in-training letter is therefore, January 5, 2022. There will be no exceptions.

Electronic Signature

Completion of all required disclosure information in the online abstract submission system serves as an agreement and is accepted in lieu of a faxed signature. It certifies the ASH abstract submitter's understanding of the rules for participation contained in the online abstract submission program and affirms that:

  1. All authors approve of submitting this work for presentation;
  2. The author(s) assign(s) copyright of the abstract to ASH upon submission (unless one of the authors is a U.S. Federal employee—in such case, ASH does not hold copyright) for use in the ASH Summit on Immunotherapies for Hematologic Diseases meeting materials. Authors retain copyright for all other uses after the meeting;
  3. All authors have read the ASH Abstract Conflict-of-Interest Policy and have acted in accordance with that policy;
  4. The author(s) agree(s) to materially confine the presentation to information in the abstract, if accepted for presentation. If an author has more than one abstract accepted, each presentation will be materially confined to the information in the abstract selected for the specific session; and
  5. The presenting author will be available to present the abstract if selected for the program. The author(s) will immediately notify ASH if the presenting author must be changed.
  6. The data in the abstract are not publicly available via major search engines; have not been accepted for publication before the abstract submission closing date; nor will they be materially presented at a meeting of 1,000 or more participants (excepting abstracts accepted for presentation or publication for the 2021 ASH Annual Meeting) before the ASH Summit on Immunotherapies for Hematologic Diseases.

Sample Abstract

A sample abstract is provided for your reference below. Note that the title, authors, and institutions are entered in separate fields in the submission form, not in the abstract body, as they are not included in the character count.

EZH2 and BCL6 Cooperate To Create The Germinal Center B-Cell Phenotype and Induce Lymphomas Through Formation and Repression Of Bivalent Chromatin Domains

Wendy Béguelin, PhD1, Matt R Teater, MS1,2, Katerina Hatzi, PhD3, Relja Popovich, PhD4, Yanwen Jiang, PhD1,2, Karen L. Bunting, PhD1, Monica Rosen1*, Hao Shen, MD1, Shao Ning Yang1, Young Rock Chung, MSc5, Rita Shaknovich, MD/PhD1, Caretha Creasy6, Randy D. Gascoyne, MD7, Leandro Cerchietti, MD3,8, Ross L. Levine, MD9, Omar Abdel-Wahab, MD5, Jonathan D. Licht, MD4, Olivier Elemento, PhD2 and Ari M. Melnick, MD3,8

1Department of Medicine/Hematology-Oncology, Weill Cornell Medical College, New York City, NY
2Department of Physiology and Biophysics and Institute for Computation Biomedicine, Weill Cornell Medical College, New York City, NY
3Department of Medicine/Hematology-Oncology, Weill Cornell Medical College, New York, NY
4Hematology/Oncology, Northwestern University, Chicago, IL
5Leukemia Service and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York City, NY
6Glaxo Smith Kline, Collegeville, PA
7Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada
8Department of Pharmacology, Weill Cornell Medical College, New York City, NY
9Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

The EZH2 histone methyltransferase is the enzymatic core of the Polycomb repressor 2 (PRC2 complex), is highly upregulated in germinal center (GC) B cells and is targeted by gain-of-function somatic mutations that enhance its ability to trimethylate histone 3 lysine 27 in diffuse large B cell lymphomas (DLBCLs) and follicular lymphomas (FLs). We explored the significance and mechanism of action of EZH2 in normal GC development and lymphomagenesis. We observed that EZH2-conditional knockout mice and mice exposed to the novel EZH2-specific inhibitor GSK503 both completely failed to form GCs or high affinity antibodies. Using ChIP-seq, sequential QChIP, RNA-seq and functional assays we demonstrated that EZH2 mediates the GC phenotype through de novo formation of bivalently marked chromatin domains (characterized by overlapping H3K27me3 repressive mark with the H3K4me3 activation mark) at the promoters of target genes involved in cell cycle regulation (e.g. CDKN1A) and in GC exit and terminal differentiation program (e.g. IRF4 and PRDM1). Notably, mutant EZH2 caused hyper-repression of these bivalent genes through increased H3K27me3, which we showed is causal to the mutant EZH2 phenotype. Mice engineered to conditionally express lymphoma-associated EZH2Y641F exhibited aberrant suppression of bivalent gene expression leading to increased proliferation, blockade of terminal differentiation, and massive GC hyperplasia. Transcriptional profiles of human DLBCL patients revealed that those with mutant EZH2 display a unique signature consisting of silencing of GC bivalent genes, suggesting that mutant EZH2 contributes to human lymphomagenesis through paralysis of bivalent chromatin domains.

This scenario is reminiscent of the role of the transcriptional repressor BCL6, which is also required for GC formation. BCL6 also represses CDKN1A, IRF4 and PRDM1 and is required to maintain the proliferation and survival of DLBCL cells. Notably BCL6 represses its targets by associating with BCoR, which forms a variant of Polycomb repressor 1 (PRC1) complex. We hypothesized that EZH2 and BCL6 cooperate to mediate the GC B-cell phenotype and when aberrantly active may cooperate to form GC-derived B-cell lymphomas. Using ChIP-seq studies we found that the target promoters of BCL6-BCoR complex (but not promoters with BCL6 complexes lacking BCoR) significantly overlap with EZH2 bivalent promoter genes in primary human GC B cells and lymphoma cells (Hypergeometric test, p=1.5x10-26). Treatment of DLBCL cells with EZH2 or BCL6 inhibitors or siRNA partially derepressed these genes indicating that both factors cooperate and are required to mediate full repression of these crucial loci. To determine whether EZH2 and BCL6 cooperate to generate GC-derived lymphomas, we transduced bone marrow of IµHABCL6 mice (which mimic BCL6 translocations in DLBCL) with retrovirus encoding mutant EZH2Y641F or GFP alone, and transplanted them into lethally irradiated recipients. Only EZH2Y641F/BCL6 mice showed an accelerated lethal phenotype (log-rank test, p=0.007), with reduced median survival (EZH2Y641F: 309 days, empty vector: 453 days). Serial bone marrow transplantation resulted in even further increased lethality (log-rank test, p=0.004; median survival EZH2Y641F: 127 days, empty vector: 169 days). Given the oncogenic cooperation between BCL6 and EZH2, we hypothesized that rational combinatorial therapy with BCL6 and EZH2 inhibitors might synergistically kill DLBCLs. Indeed, by combining the EZH2 inhibitor GSK343 and the RI-BPI, a drug that inhibits BCL6 by abrogating its interaction with BCoR, we observed a potent synergistic effect on the inhibition of DLBCL cell lines proliferation. The combination of these two inhibitors in mice bearing DLBCL xenografts accordingly suppressed tumor growth more effectively than either agent alone. Finally, the combination also yielded further killing of primary human DLBCL cells growth in a co-culture system that we developed for testing primary human specimens.

In summary we identified the first epigenetic mechanism of lymphomagenesis involving aberrant repression of GC-specific bivalent domains by EZH2 (PRC2) in cooperation with BCL6-BCoR (PRC1) complexes, as well as a rational epigenetic-based and molecular targeted therapeutic approach with the potential to eradicate lymphomas without harming normal tissues.

Embargo Policy

Abstracts submitted to the ASH Summit on Immunotherapies for Hematologic Diseases are embargoed from the time of submission until the abstract is presented at the Summit.

  • For poster presentations, the embargo lifts when the poster session containing the poster opens for viewing.
  • For oral/invited presentations, the embargo lifts at the start time of the session in which the presentation is being made.
  • Prior to the embargo being lifted, the first author, co-authors, and sponsor of the abstract must not:
    • Publish the information or provide it to others who may make it publicly available. (This includes posting the title of an accepted abstract on social media.)
    • Release the research/study to news media, or
    • Use the information for trading in the securities of any issuer or provide it to others who may use it for securities-trading purposes.
  • An exception may be granted in cases in which the Securities and Exchange Commission (SEC) requires a press release to comply with security laws. ASH will consider such requests on an ad hoc basis. More information on requesting such an exception can be found on the ASH website.
  • Authors must notify ASH if a manuscript based on the abstract is accepted for journal publication. Publication before the Summit, including early publication of an accepted manuscript, may result in the abstract being removed from the Summit.
  • If the Embargo Policy is violated, the abstract may be withdrawn by ASH from presentation at the Summit.

Abstracts accepted by ASH for presentation or publication for the 2022 ASH Annual Meeting are exempted from the above restrictions.

Note: Abstracts submitted to the ASH Summit on Immunotherapies for Hematologic Diseases are eligible to be re-submitted to the 2023 ASH Annual Meeting; however, any of the following criteria will make an abstract ineligible for presentation at the ASH 2023 Annual Meeting:

  • Data are publicly available via major search engines (such as PubMed, Google Scholar, etc.) prior to the annual meeting abstract submission deadline.
  • Data have been accepted for publication before the annual meeting abstract submission deadline.
  • Data have been or are to be presented at a meeting of 1,000 or more participants (excluding the ASH Summit on Immunotherapies for Hematologic Diseases) before the 2023 ASH Annual Meeting and Exposition.

Contact Information

Send related correspondence and questions regarding abstract submissions or notifications to [email protected].

ASH Summit on Immunotherapies for Hematologic Diseases Registration and Housing

  • Please note that submitting an abstract does not register you for the ASH Summit on Immunotherapies for Hematologic Diseases.
  • To register, you must complete and return an Attendee Registration Form, or register online.