American Society of Hematology

Information for Late-Breaking Abstract Authors

The 60th ASH Annual Meeting will be held December 1-4, 2018, in San Diego, CA. The goal of the ASH annual meeting is to present the best new scientific research in all areas of hematology.

The ASH Program Committee recognizes that the results of some exciting research may not be available by the general abstract submission deadline. Hence, ASH offers a call for late-breaking abstract submissions for abstracts that highlight novel and substantive studies of high impact. The goal is to enrich the ASH annual meeting with outstanding studies that are completed after the general abstract submission deadline.

All abstract submissions must be made electronically through ASH’s online abstract submission system. The late-breaking abstracts site opens on October 18, 2018, and the deadline for late-breaking abstract submission is October 30, 2018, at 11:59 p.m. PDT.

Notification regarding acceptance or rejection of abstracts will be sent to the presenting author on or after November 18, 2018. Abstracts accepted for presentation at the meeting will be published November 20, 2018.

Eligibility

To submit a late-breaking abstract, the following criteria must be met:

  • Late-breaking abstracts should highlight novel and substantive studies of high impact. The late-breaking abstract deadline is not intended to be merely an extension of the general submission deadline and will focus on capturing abstracts with ground-breaking and novel data that otherwise could not be presented at the annual meeting.
  • The selection process will be highly competitive; no more than six abstracts will be selected for an oral presentation in a late-breaking abstracts session on Tuesday morning of the ASH annual meeting.
  • Examples of suitable late-breaking abstracts might include the results of a practice-changing prospective clinical trial or the discovery of a mechanism underlying or characterizing a disease process (such as the JAK2 mutation in myeloproliferative disorders), which were not fully available by the general abstract submission deadline.
  • Late-breaking abstracts are not eligible for oral or poster presentation in the regular ASH annual meeting abstract program. Late-breaking abstracts will not be chosen from among the abstracts submitted by the general submission deadline, but all other ASH policies stated in the general submission call for abstracts will still apply.
  • The accepted late-breaking abstracts will be published online on the meeting website on November 20, 2018, and in the Blood Abstracts November supplement.
  • At least one of the authors must be an ASH member who has paid the current membership dues.
  • If none of the abstract authors is an ASH member, the abstract must be sponsored by a current ASH member. ASH members are urged to use their best judgment in restricting sponsorship to a reasonable number of abstracts, keeping in mind that they are endorsing the authenticity and quality of each abstract that they sponsor.
  • Research and/or studies must fit into one of the ASH 2018 Abstract Review Categories

Any of the following criteria will make a late-breaking abstract ineligible for presentation at the ASH annual meeting:

  • 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 2018 ASH Annual Meeting*;
  • Data are to be presented at an ASH Friday Satellite Symposium.

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.

*Note: Abstracts submitted to other ASH meetings (e.g., the ASH Meeting on Hematologic Malignancies) are exempted from the above meeting-size restriction and are eligible to be re-submitted to the 2018 ASH Annual Meeting.

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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 "Contact Information" 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 and the Accreditation Council for Continuing Medical Education (ACCME) Standards for Commercial Support for Continuing Medical Education (CME).
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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.
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General Guidelines

  • The abstract must address scientific questions, detail clinical observations, or contain primary scientific data.
  • Abstracts submitted to ASH 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 annual meeting until the meeting is concluded. (Note the of the Call for Late-Breaking 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). This means that the identical abstract may not be republished or submitted to another 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 $125 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 annual meeting; therefore, all authors planning to attend the ASH annual meeting must register for the meeting.
  • No revisions can be made after the abstract submission deadline.
  • The presentation at the annual meeting must reflect the submitted abstract. In particular, the abstract title, authorship, and scientific content of the presentation at the annual 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.
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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 mid-November 2018.
  • 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 subject 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.
  • Of all late-breaking abstracts submitted for consideration, only six will be considered for an oral presentation. All other abstracts will be rejected and not published. The Late-Breaking Session features the top six abstracts. These are formal oral presentations, each followed by a brief discussion.

Acceptance/Rejection Notification

  • Notification regarding acceptance or rejection of abstracts will be sent to the presenting author by November 18, 2018 by email; consequently, an accurate email address is critical. If you have not received an email notification by November 18, 2018, contact ASHabstracts@hematology.org. Rejection notifications will also be sent at that time.
  • The decision of the ASH Abstract Reviewers regarding acceptance and presentation of late-breaking abstracts is final.
  • 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 ash@confex.com and ASHabstracts@hematology.org 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 both the confex.com and hematology.org domains are added to your email address whitelist.
  • The decision of the ASH Program Committee regarding acceptance and presentation of abstracts is final.
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Abstract Withdrawal

  • Authors can withdraw the late-breaking abstracts by the submission deadline of October 30, 2018. 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, have been deemed scientifically unsound, or have been found to include inaccurate data, etc.
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Publication of the Late-Breaking Abstracts

  • The six late-breaking abstracts accepted for presentation at the ASH annual meeting will be published online on November 20, 2018, as part of the online annual meeting program, as well as in the special online-only November supplemental issue of Blood.
  • Late-breaking abstracts not accepted for presentation will not be published in any form.
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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 that might be construed as resulting in an actual, potential, or apparent conflict.
  • ASH abides by rules formulated by the Accreditation Council for Continuing Medical Education (ACCME) that require that you disclose any relevant financial relationship you or your spouse/partner have had within the past 24 months. For this purpose, "relevant financial relationships" are those from which you have received or may receive financial benefit and which are related to the CME content.
  • As a continuing medical education (CME) provider accredited by the ACCME, ASH must ensure balance, independence, objectivity, and scientific rigor in all presentations at the ASH annual meeting.
  • 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.
  • Appropriate disclosure will be stated in the special online-only abstract issue of Blood. Abstracts will not be considered for the program without completion of disclosure information for all of the authors.

Author Responsibility Regarding Conflict-of-Interest Disclosure

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

When to Disclose
Please disclose any relationships or circumstances that might affect or appear to affect the research presented. These relationships include you or any individual with whom you directly share income.

What to Disclose
You must disclose the relationship and state the name of the 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 note that there is no information to disclose or to provide disclosure information pertinent to the abstract. Disclosed information pertinent to the abstract may include the following areas:

  • Employment
  • Consultancy
  • Ownership interests (including stock options) in a start-up company, the stock of which is not publicly traded
  • Ownership interest (including stock options, but excluding indirect investments through mutual funds and the like) in a publicly traded company
  • Research funding
  • Honoraria directly received from an entity
  • Patents and royalties
  • Paid expert testimony
  • Membership on an entity's board of directors, speakers bureau, or its advisory committees
  • Any other financial relationship

Off-Label Use
You will be required to note whether your presentation will include discussion of off-label use of products. If so, you must provide a brief explanation.

Other Areas
During the disclosure submission process, you will also be required to indicate your compliance with the following:

  • If you are providing recommendations involving clinical medicine, these recommendations will be based on evidence that is accepted within the profession of medicine as adequate justification for their indication and contraindications in the care of patients. All scientific research referred to in support of a patient-care recommendation will conform to generally accepted standards of experimental design, data collection, and analysis.
  • The content of the information with which you are involved will promote quality in health care or advances in science and will not promote a specific proprietary or commercial interest. Content for this publication will be well-balanced and unbiased.
  • If you have been trained or utilized by a commercial entity or its agents as a speaker (e.g., participation in a speakers bureau) for any commercial interest, the promotional aspects of that work must not be included in the presentation in any way.

Embargo Policy

  • Abstracts submitted to the ASH annual meeting are embargoed from the time of submission.
  • For the research to be eligible for presentation at the ASH annual meeting, information contained in the abstract, as well as additional data and information to be presented about the research at the annual meeting, may not be made public before the abstract has been published/presented at the ASH annual meeting.
  • 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.
    • 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 Corporate-Institutional Press Policies page.
  • Authors must notify ASH if, after the submission deadline, the data are accepted for publication and will be published online or in print before the ASH annual meeting. Publication before the meeting may result in the abstract being removed from the meeting.
  • If the Embargo Policy is violated, the abstract may be withdrawn by ASH from presentation at the annual meeting and from publication.
  • View more detailed information about the Society's Embargo Policy. Please contact ASH Communications Specialist Stephen Fitzmaurice at sfitzmaurice@hematology.org or 202-552-4927 with any questions.

ASH Statement on Commercial Interest Presenters
The primary purpose of the ASH Continuing Medical Education 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 learners and to serve the public interest, the content of ASH CME may include information planned, presented, or authored by employees of commercial interests. ASH is committed to the integrity of the science presented at its CME 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. ASH maintains control of all content and plans all of its activities in compliance with the ACCME Standards for Commercial Support.

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How to Submit a Late-Breaking Abstract

The deadline to submit late-breaking abstracts has now passed.

All abstracts must be submitted by October 30, 2018, at 11:59 p.m. Pacific Time. Submissions that are incomplete by the deadline will be rejected.

  • Late-breaking Abstracts must be submitted online through the official online abstract submission system. Emails and word processing files not submitted through the site will not be accepted.
  • There is a $125 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 the annual meeting; therefore, all authors planning to attend the ASH annual meeting must register for the meeting.
  • Electronic submission works optimally with Microsoft Internet Explorer 7+, Mozilla Firefox 3.0+, and Safari or MAC OS 10.4+. Netscape Navigator 7.7+ is supported, but its use is discouraged, since not all features are available. The online abstract submission system will provide links so that you can download free browser software.
  • If this is the first time that you are submitting an abstract for the ASH annual meeting, please be sure to check the box that indicates this during submission.
  • 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 October 30, 2018, at 11:59 p.m. PDT. 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 ash@confex.com.
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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.
  • If none of the abstract authors is an ASH member, the program will ask you to provide the name of the ASH member who is sponsoring the abstract.

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

    • All authors must assign copyright of the abstract to ASH, unless one of the authors is a U.S. Federal employee (in such case, ASH does not hold copyright).

    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 submitted for the ASH annual meeting are published in a special, online-only November supplemental issue of Blood, the Journal of the American Society of Hematology. 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. This includes the author list.
    • 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. Pay careful attention to superscripts, type case font sizes, and special characters when uploading abstract text.
    • Use numerals to indicate numbers, except when beginning sentences.
    • All 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. An image can also be created by exporting your table in MS WORD to PDF format and then converting the file to an image.
    • Any references should be noted as citations within the text and not as footnotes at the end of the abstract text.

    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. Please note that some categories have been restructured.
    • 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.
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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 and publication;
  2. The author(s) transfer(s) all copyright ownership of the named abstract to the American Society of Hematology (except when one or more authors are U.S. Government employees);
  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;
  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; and
  6. The data in the late-breaking 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 before the ASH annual meeting (note the exception for abstracts submitted to other ASH meetings in the Eligibility section above); and are not to be presented at an ASH Friday Satellite Symposium.
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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.

The LRF/ZBTB7A Transcription Factor Is a BCL11A-Independent Repressor of Fetal Hemoglobin
Takeshi Masuda, PhD1, Xin Wang, PhD2, Manami Maeda, MD, PhD1, Matthew C. Canver, BS3, Falak Sher, PhD3, Alister P.W. Funnell, PhD4, Chris Fisher, PhD5, Maria Suciu5, Gabriella E. Martyn4, Laura J. Norton4, Ruijia Zhu1, Ryo Kurita, PhD6, Yukio Nakamura, MD, PhD6, Jian Xu, PhD7, Douglas R. Higgs, FRS5, Merlin Crossley, DPhil4, Daniel E. Bauer, MD, PhD3, Stuart H. Orkin, MD8, Peter V. Kharchenko, PhD2 and Takahiro Maeda, MD, PhD1
1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
2Department of Biomedical Informatics, Harvard Medical School, Boston, MA
3Pediatric Hematology-Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
4School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
5MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, United Kingdom
6Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Japan
7Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX
8Department of Pediatric Hematology-Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Induction of fetal-type hemoglobin (HbF: α2γ2) is a promising means to treat hemoglobinopathies; however, precisely how HbF expression is silenced in adult erythroid cells is not fully understood. Such knowledge is essential to develop mechanism-based, targeted approaches to reactivate HbF production. Here, we show that Leukemia/lymphoma Related Factor (LRF), encoded by the ZBTB7A gene, is a novel and potent repressor of HbF production.

To assess the effects of LRF loss on the mouse erythroid transcriptome, we performed RNA-Seq analysis using splenic erythroblasts from control and LRF conditional knockout (Zbtb7aF/F Mx1-Cre+) mice. LRF-deficient adult erythroblasts showed significant induction of Hbb-bh1, but not Hbb-y. The results were validated at the protein levels via isoelectric focusing of peripheral blood (PB) hemolysates and MALDI-TOFMS analysis. LRF loss also reactivated human fetal globin expression in vivo in LRF conditional KO mice harboring the human β-globin gene cluster as a yeast artificial chromosome transgene (β-YAC).

To determine whether LRF loss could induce HbF in human erythroid cells, we employed human CD34+ hematopoietic stem and progenitor (HSPC)-derived primary erythroblasts and determined γ-globin expression levels upon shRNA-mediated LRF knockdown (KD). HbF levels in LRF KD cells (49-70%) were much greater than those seen in parental or scrambled-shRNA transduced cells. We next employed a novel human immortalized erythroid line (HUDEP-2). This line possesses an advantage over lines currently used for globin switching studies because it expresses predominantly adult hemoglobin (HbA: α2β2), with very low background HbF expression. Using CRISPR/cas9 gene modification, we knocked out ZBTB7A in HUDEP-2 cells and performed RNA-Seq analysis. As expected, γ-globin (HBG1 and HBG2) transcripts, but not those of embryonic ε-globin (HBE1), were markedly induced in ZBTB7A KO (ZBTB7AΔ/Δ) HUDEP-2 cells. ZBTB7AΔ/Δ cells exhibited HbF levels greater than 60%, while that of parental cells was less than 3%. Notably, the HbF reactivation occurred without changes in levels of transcripts encoding known HbF repressors, including BCL11A, the principal known switching factor.

We next performed chromatin-immunoprecipitation and sequencing (ChIP-Seq) with an anti-LRF antibody using HSPC-derived proerythroblasts and HUDEP-2 cells. The most enriched motif identified in either was concordant with that previously identified in vitro using CAST analysis (Maeda et. al. Nature 2005), confirming antibody specificity. Supporting a direct role of LRF at the β-globin cluster, we observed several significant enrichment of LRF-ChIP binding signals at adult (HBB), fetal (HBG1) globin loci and the upstream hypersensitivity (HS) sites within the locus control region (LCR). ATAC-Seq (for assay for transposase-accessible chromatin with high-throughput sequencing) analysis revealed strong chromatin accessibility at the γ-globin locus in ZBTB7AΔ/Δ cells. Strikingly, differential enrichment of ATAC-signals in ZBTB7AΔ/Δ cells was evident only at the γ-locus. Thus, while LRF binds to the HBB locus and HS sites as well as to the HBG1 locus, LRF depletion specifically opens chromatin at the γ-globin locus.

Finally, to determine whether LRF and BCL11A suppress γ-globin expression via distinct mechanisms, we established LRF/BCL11A double knockout HUDEP-2 cells. Strikingly, HUDEP-2 lines lacking both LRF and BCL11A exhibited almost a complete switch in expression from adult- to fetal-type globin, suggesting that these two factors cumulatively represent the near entirety of γ-globin repressive activity in adult erythroid cells. Our findings reveal a novel molecular mechanism regulating γ-globin silencing and may open a new window for therapeutic targeting in the treatment of hemoglobinopathies.

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Contact Information

Send related correspondence and questions regarding abstract submissions or notifications to: ASHabstracts@hematology.org.back to top

ASH Annual Meeting Registration and Housing

Please note that submitting an abstract does not register you for the ASH annual meeting. To register, you must complete and return an Attendee Registration Form or register online. back to top