Foundation for Burkitt Lymphoma

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The Foundation for the Burkitt Lymphoma Research 2024 Annual Report and 15 Years of Scientific Research in Burkitt Lymphoma

The Foundation for Burkitt Lymphoma Research was established in late 2009 by Dr. Jean Paul Martin and Dr. Marie-Reine Martin.  They took this decision because their son, Xavier Martin, had been diagnosed with Burkitt Lymphoma, and passed away from a relapse of the disease in May 2010.

During the past fifteen years the Foundation undertook and successfully completed a number of important activities which have contributed to a better understanding of the genomic structure and pathophysiology of Burkitt Lymphoma.  During this time period 282 patients as well as 93 research professionals, representing 28 global institutions, contributed to this body of work.

This special yearly report will summarize, and in some instances provide detailed content of the activities and outcomes that occurred during the past 15 years.  In other words, it will “Tell the Story” of the Foundation and the goals and objectives it established and accomplished, and the significant genomic results obtained.  Content will be provided under the following headings:

  1. FOUNDATION FRAMEWORK, SCIENTIFIC ADVISORY BOARD, GOALS
  2. PARTNERSHIP WITH THE FOUNDATION FOR THE US NATIONAL INSTITUTES OF HEALTH AND THE NATIONAL CANCER INSTITUTE.
  3. DEVELOP A CLINICAL TRIAL PROTOCOL TO STUDY AND CHARACTERIZE THE GENOMIC STRUCTURE OF BURKITT LYMPHOMA, RECRUIT GLOBAL INVESTIGATORS/STUDY SITES, LAUNCH THE STUDY: BURLITT LYMPHOMA GENOME SEQUENCING PROJECT (BLGSP)
  4. WEBSITE: FOUNDATIONFORBURKITTLYMPHOMA.ORG
  5. KEY FINDINGS FROM THE BLGSP
  6. SUPPORT FOR DR. RYAN MORIN’S LABORATORY
  7. FUTURE
  8. CONTRIBUTOR ACKNOWLEDGEMENT

 

1. FOUNDATION FRAMEWORK, SCIENTIFIC ADVISORY BOARD, GOALS: 

The Foundation is registered and located in Geneva, Switzerland.  It is governed by a Council:  Chairman and President, Dr. Jean Paul Martin; Vice President, Dr. Marie-Reine Martin; Secretary, Katell Bassou; Treasurer, Marc Winteler; Member, Olivier Bassou

The Foundation Executive Director is Dr. John D. Irvin.  Strategic Plans were developed by the Council and Dr. Irvin in 2010 and 2015.

At the launch of the Foundation, in order to develop and prioritize key strategic goals and objectives, a global, expert panel was recruited to serve as a Scientific Advisory Board (SAB).  These individuals were selected based upon their expertise in the science of Burkitt Lymphoma (BL):  pathology, genomics, clinical trial design and methodology, genome sequencing and analysis, data management, patient care and treatment.  Members of the SAB include:  Dr. Corey Casper, Access to Advanced Health Institute, Seatle; Dr. Riccardo Dalla-Favera, Columbia University Medical Center, New York City; Prof. Gerard Evan, Cambridge University; Prof. John Gribben, Barts and the London School of Medicine; Dr. Ryan Morin, Simon Fraser University; Dr. Charles Mullighan, St. Jude; Dr. Ariela Noy, Sloan Kettering Cancer Institute; Prof. Eric Oksenhendler, Hospital Saint-Louis, Paris; and Dr. Louis Staudt, National Cancer Institute.  Prof. Jane Apperley, Hammersmith Hospital, London; and Dr. Marco Marra, British Columbia Cancer are Emeritus members of the SAB. 

The Foundation held annual face-to-face meetings, mid-year update teleconferences with the SAB, and ad-hoc telephone calls with the individual members.  The decisions and actions of the SAB were documented in meeting minutes and in the Foundation Annual Reports.

At the first Annual Meeting of the SAB in December, 2009, the discussions focused on potential goals and objectives for the Foundation.  It was determined that the key goal would be to develop information that would “further the understanding of the pathophysiology of Burkitt Lymphoma” and the objective to accomplish this goal would be to conduct a large, global clinical trial in both pediatric and adult BL patients, including all subtypes of the disease:  endemic, sporadic, HIV-associated.  The trial would be the first study to explore whole genome sequencing and clinical characteristics in all subtypes of the disease, and be titled   the Burkitt Lymphoma Genome Sequencing Project (BLGSP).  As noted, the SAB met face-to-face on an annual basis to discuss and make decisions regarding the progress of the study.  The mechanics of the study will be presented in a subsequent section of this paper.

A second goal was established, to “facilitate the exchange and collaboration of data with the global scientific community”; objectives were to develop and publish abstracts, manuscripts, and presentations from the BLGSP and other data sets.

 

2. PARTNERSHIP WITH THE FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH (FNIH) AND THE NATIONAL CANCER INSTITUTE (NCI): 

At the Strong recommendation of the Scientific Advisory Board, especially from Dr. Louis Staudt and Dr. Riccardo Dall-Favera, the Foundation initiated a process to establish a working relationship with the Foundation of the National Institutes of Health and the National Cancer Institute.  The first step was to develop and sign a Letter of Intent, followed by the three parties signing a Memorandum of Understanding.  This process enabled the Foundation to collaborate actively with the NCI’s Department of Genomics.  (The Foundation contributed by making a generous initial donation to the BLGSP). 

 

3. DEVELOP CLINICAL TRIAL PROTOCOL TO STUDY AND CHARACTERIZE THE GENOMIC STRUCTURE OF BURKITT LYMPHOMA, RECRUIT GLOBAL INVESTIGATORS/STUDY SITES, LAUNCH THE STUDY: BURKITT LYMPHOMA GENOME SEQUENCING PROJECT (BLGSP):

Working with the NCI Director of Genomics, Dr. Daniella Gerhard, and her staff, the Foundation assisted with the development of the clinical protocol and case report forms, and in recruiting investigator sites for the BLGSP.

The objective of the protocol was to determine and compare the molecular characterization, using whole genome sequencing, of both pediatric and adult patients with various subtypes of BL (endemic, sporadic, HIV associated) with a matched demographic group (typically known as a control group).  The protocol was approved by the NCI and the individual investigator Institutional Review Boards.

As noted, the Foundation also assisted in researching and recruiting study investigation and research sites in the US, Europe, and Sub-Sahara Africa.  The study Investigators and their Institutions/location included:  Dr. Jeremy Abramson, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston; Dr. Corey Casper, Access To Advanced Health Institute and University of Washington, Seatle; Dr. Alina Gerrie, BC Cancer and University of British Columbia, Vancouver; Dr. Fabio Leal, Brazilian Cancer Institute; Dr. Sam Mbulaiteye, NCI and EMBLEM Trial; Dr. Charles Mullighan, St. Jude Children’s Research Hospital, Memphis; Dr. Ariela Noy, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York City; Dr. German Ott, Robert Bosch Kranenhaus, Stuttgart; Prof. Gilles Sales, University Claude Bernard, Lyon;  Dr. David Scott, BC Cancer and University of British Columbia, Vancouver; Dr. Wyndham Wilson, NCI.

The first patients were enrolled in the BLGSP beginning in January, 2011.  Dr. Gerhard developed and chaired the BLGSP Working Group, which met monthly to discuss enrollment, and reach decisions regarding all aspects of the conduct, data management and analysis of the BLGSP.  Members of this Working Group included the Executive Director of the Foundation, NCI project management, members of the Central Pathology Review Committee, the data processing group, and staff of the genome sequencing laboratory of Dr. Ryan Morin, Simon Fraser University.  At each annual meeting of the SAB, Dr. Gerhard summarized the status of the BLGSP and discussions/decisions by the Working Group. 

 

4. FOUNDATION WEBSITE:

The Foundation Website, www.foundationforburkittlymphoma.org, was designed and launched in 2016, and updated periodically.  It contains key, detailed information about the Foundation, Burkitt Lymphoma, and the Burkitt Lymphoma Genome Sequencing Project.

Readers can learn about Burkitt Lymphoma in the “Quick Start Guide” written by Dr. Jean Paul Martin and Dr. Marie-Reine Martin.  They can also review brief biographies of all the key contributors to the Foundation and BLGSP:  members of the Foundation Council and the Executive Director; Scientific Advisory Board members; BLGSP Steering Committee members; Central Pathology Review Committee, and the Clinical Investigators.    

Individuals who visit the site, as an example, can also review the specific details of the BLGSP protocol, and under the “News” tab review all the published Abstracts, key Presentations, and Manuscripts describing the findings from this landmark study, as well as accompanying Commentaries.  A summary of the findings from the BLGSP is provided in the next section of this paper.

In order to honor the memory of Dr. Daniela S. Gerhard, who suddenly and unexpectedly passed away in June 2021 the Foundation created a Memorial Plaque dedicated to our dear friend and former colleague.  This Plaque was presented by the Foundation to the Office of Cancer Genomics at NCI.  A picture of the Memorial Plaque is included on the website with her biography.

 

5. KEY FINDINGS FROM THE BURKITT LYMPHOMA GENEOME SEQUENCING PROJECT:

The BLGSP began enrollment of pediatric and adult Burkitt Lymphoma patients in early 2011, and completed enrollment until 2021.  During this period of 10 years a total of 181 pediatric BL and 101 adult BL patients were enrolled in the study.

The initial publication from the BLGSP appeared in the journal Blood on March 21, 2019, and was entitled:  Genome-Wide Discovery of Somatic Coding and Noncoding Mutations in Pediatric Endemic and Sporadic Burkitt Lymphoma.  The first author on the publication is Dr. Bruno Grande, who was a Ph.D. candidate in Dr. Ryan Morin’s Laboratory at Simon Fraser University at the time.  A Commentary by Professor Jonathan Streford and Professor David Osler accompanied the publication.  The Foundation Website www.foundationforburkittlymphoma.org contains both documents in the “News” tab,

Using whole-genome and transcriptome analysis, with sophisticated computational biology to compare the molecular landscape of pediatric Burkitt Lymphoma, the study found: “Tumor EVB status is more strongly associated with distinct genetic and etiological mechanisms than geographic origin, and EBV-positive BL genomes feature fewer driver mutations despite their greater mutational load that is partly a result of increased AICAD activity”.

The second major manuscript from the BLGSP was published in Blood February 23, 2023.  The manuscript is entitled:  Genetic Subgroups Inform on Pathobiology in Adult and Pediatric Burkitt Lymphoma.  The manuscript is dedicated to Dr. Daniela Gerhard. The first author is Dr. Nicole Thomas, also a Ph.D. candidate in Dr. Morin’s Laboratory at the time.  The publication was accompanied by a Commentary written by Dr. Adam J. Olszewski.  Both documents can be found on the Foundation’s Website.

As summarized, findings from this Publication using whole genome sequencing analysis of 181 pediatric and 100 adult BL cases, demonstrate both data sets share a common pathobiology with Epstein Barr Virus, influencing the genetic and molecular profiles in both entities.  Further BL can be robustly divided into three genetic subgroups with distinct molecular underpinnings.

In his Commentary, Dr. Olszewski complemented the work in the study and noted that future work in BL would require prospectively collected samples from patients who are uniformly treated in clinical trials in order to examine the prognostic impact of specific genomic alterations in BL, and the practical relevance of the subgroups.

A third manuscript entitled:  DNA Methylation based Burkitt Lymphoma Epitypes with Distinct Molecular and Clinical Features, was submitted for publication in late 2024.  Dr. Nicole Thomas is the lead author on that Manuscript.

In addition to the three manuscripts, presentations and abstracts were delivered at several scientific meetings over the course of conduct of the BLGSP.  A poster presentation was given by Dr. Daniela Gerhard at the 2016 annual meeting of the American Society of Hematology (ASH).  Others included: a presentation by Dr. Bruno Grande at the November 2017 11th International Conference on Cancer in Kigah, Rwanda; Dr. Grande also gave a presentation at the 2017 annual meeting of ASH; Dr. Nicole Thomas gave an abstract presentation at the 16th annual meeting of the International Conference on Malignant Melanoma in June 2021; Dr. Kostia Dreval presented an abstract at the virtual 16th meeting of the International Conference on Malignant Lymphoma, June 2021; Dr. Thomas presented an abstract at the December 2021 ASH meeting; and she published an abstract  in Blood, November 2022.

 

6. SUPPORT FOR DR. RYAN MORIN’S LABORATORY:

In addition to financial support of the Burkitt Lymphoma Genome Sequencing Project, the Foundation provided support for Dr. Ryan Morin’s Laboratory in the Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.  This support was structured as a Fellowship.  Recipients included Dr. Bruno Grande when he was a Ph.D. candidate; Dr. Nicole Thomas when she was a Ph. D. candidate; and Dr. Kostia Dreval a post-doctorial scientist who worked on the BLGSP.

 

7. FUTURE:

The Foundation is considering providing support to Dr. Ryan Morin’s Laboratory for a new research project, which is consistent with the research mission of the Foundation, probably in cosponsor ship with “Genome British Columbia”.

 

8. CONTRIBUTOR ACKNOWLEDGEMENT:

The Foundation is deeply grateful and appreciative of the outstanding work performed by all the individuals who contributed their time and expertise to assuring the success of the Burkitt Lymphoma Genome Sequencing Project.  For many, their commitment for over a decade is testimony to their passion for developing a better understanding of Burkitt Lymphoma.  The Foundation is also most appreciative to the patients who participated in the project, their supportive families, and to the administrative staffs who facilitated the project.

Following is an alphabetical listing of the individuals and their respective institutions.

Access to Advanced Health Institute, Seattle, Washington, USA:  Corey Casper

British Columbia Cancer Agency, Vancouver, Canada:  Pedro Farinha; Alina Gerrie; Laura K. Hilton; Yussanne Ma; Marco A. Marra; Andy Mungall; Karen Mungall; Karen Novik; David Scott; Graham Slack; Jasper Wong

Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA:  Maureen Dyer

George Washington University, Washington, DC, USA:  Jeffrey Bethony, Kishor Bhata; Kerion Dunleavy

Hospices Civils de Lyon, Univ. Lyon, Sud, France:  Alexandra Traverse-Glehen, Gilles Sales

Hospital of Cook County, Chicago, Illinois, USA:  Paul Rubenstein

Institute of Clinical Pharmacology, Stuttgart, Germany:  German Ott

Instituto Nacional De Cancer Jose de Alencar, Rio de Janeiro, Brazil:  Fabio Leal, Robert Yarchoan

Josep Carreras Research Institute, Barcelona, Spain:  Manel Esteller, Carlos A. Garcia-Prieto

Lantem Pharma, Inc., Dallas, Texas, USA:  Kishar Bhatia

Massachusetts General Hospital, Boston, Massachusetts, USA:  Jeremy S. Abramson; Nancy Lee Harris

Memorial Sloan Kettering Cancer Center, New York City, New York, USA:  Ariela Noy

National Cancer Institute, Bethesda, Maryland, USA:  Tanja M. Davidsen; Daniela S. Gerhard; Patee Gesuwan; Nicholas B. Griner; Thomas Gross; Yiwen He; Rebecca Huppi; Elaine S. Jaffe; Sam M. Mbulaiteye; Mosta Fanokta; Ronald Mitsuyasu; Vivian Morris; James Phelan; Stefania Pittaluga; Roland Schmitz; Louis Staudt; Wyndham Wilson; Robert Yarchoan; Jean C.  ZenKlusen

National Institute of Allergy and Infectious Disease, Bethesda, Maryland, USA:  Stephen Reynolds

Nationwide Children’s Hospital, Columbus, Ohio, USA:  Hilary Allen; Jay Bowen; Anthony C. Bryan; Julie M. Gastier-Foster; Hilary Petrello

Sage Bionetworks, Seattle, Washington, USA:  Bruno Grande

Sidney Kimmel Cancer Center, Johns Hopkins Univ., Baltimore, Maryland, USA:  Richard F. Ambinder

Simon Fraser Univ., Burnaby, Canada:  Manuela Cruz; Kostia Dreval; Ryan Morin,  Nicole Thomas

St. Jude Children’s Hospital, Memphis, Tennessee, USA:  Thomas Alexander, John Kim Choi; Charles G. Mullighan; Andren J. Mungall; John T. Sandlund

Tygerberg Academic Hospital and Stellenbosch Univ., Cape Town, South Africa:  Gerard Sissolak

Uganda Cancer Institute, Kampala, Uganda:  Innocent Mutyaba; Constance Namirembe; Martin Ogwang; Abraham Omoding; Jackson Orem

Univ. of California Los Angeles, Los Angeles, California, USA:  Ronald Mitsuyasu

Univ. of Miami, Miami, Florida, USA:  Juan Carlos Ramos

Univ. of Nebraska Medical Center, Omaha, Nebraska, USA.:  Timothy C. Greiner

Univ. of North Carolina, Chapel Hill, North Carolina, USA:  Dirk Dittmer; Michael Lee

Univ. of Pennsylvania, Philadelphia, Pennsylvania, USA:  Stephen Barta; David Henry;  Rebecca Huppi

Univ. of Pittsburg School of Medicine, Pittsburg, Pennsylvania, USA:  Steven Swedlow

Washington University, St. Louis, Missouri, USA:  Nancy Bartlett; Lee Ratner

Weil Cornell Medicine, New York City, New York, USA:  Ethel Cesarman; Amy Chadburn

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