Research

Hematopoietic Development and Malignancy Program

Overview

About the HDMP

The Hematopoietic Development and Malignancy Program has a strong track record of innovation and success in combating diseases of the blood. We’ve made history: we completed the first whole-genome sequence of a cancer patient, an individual with leukemia, in 2008, published the first study comparing cancer patient genomes, and were the first to use genetic sequencing to make a clinical decision about a patient.

Today, we continue to push the boundaries of blood cancer science. We make vital contributions to emerging fields of treatment, such as targeted therapy, immunotherapy, and cellular therapy, and we work to get new drugs approved by the FDA. Through our research and clinical trials, we advance the standard of patient care.

For researchers

Program Leaders: Daniel Link, MD, and Peter Westervelt, MD, PhD 

The Hematopoietic Development and Malignancy Program (HDMP) includes 57 Washington University faculty members from four departments. The long-term goals of the HDMP are to elucidate basic mechanisms regulating normal and malignant hematopoiesis and use this information to develop strategies for the prevention, diagnosis, prognostic stratification and treatment of hematopoietic malignancies. We have identified areas of institutional strength and developed the following specific translational goals:

  • To leverage local expertise in cancer genomics to identify key genetic and epigenetic alterations in hematopoietic malignancies and develop their translational potential
  • To develop fundamental discoveries in immunology into novel immunotherapies for hematopoietic malignancies
  • To translate fundamental discoveries in stem cell biology into novel strategies to treat hematopoietic malignancies and/or improve stem cell transplantation
  • To expand translational research in multiple myeloma and lymphoma

The HDMP fosters collaborative translational research and provides training of junior investigators through research seminars, journal clubs, work-in-progress meetings and the annual HDMP retreat.

For patients

Our research translates into superior patient care that draws upon our discoveries in the laboratory. When you are treated for hematologic cancer by a member of our program, you will have access to a wide range of clinical trials for new therapies, treatments, and procedures. Your physicians will make decisions based upon a deep, molecular understanding of the conditions that they treat and study. You can also contribute to our research by donating tissue samples to one of our tissue banks, allowing our physicians and scientists to carry on their critical work.

Facts and figures

  • Program members have 243 funded projects, totaling $30.85 million in costs.
  • Our researchers have brought in $9.17 million from the NCI and $5.05 million from other peer-reviewed research projects.
  • Members contributed to 182 publications in 2018.
  • We accrued 1185 patients to clinical trials in 2017, including 534 to interventional and 651 to non-interventional studies.
  • 138 of our interventional accruals were early phase (26%) and 226 (42%) were to institutional studies.

Join us

We welcome new members through our fellowship and postdoctoral programs.

  • Fellowships: Medical fellows find that our program offers a lively space of discovery and collaboration. Learn more about our program here.
  • Postdocs: We are always seeking new postdoctoral colleagues. To inquire about a position, you can contact the PI you wish to work with, or email Brittni Black at brittniblack@wustl.edu for information about postdoctoral opportunities across the HDMP.

Donate

We are grateful for the support of donors who contribute to our research. Click here to make a donation, and be sure to specify that you would like your gift to go to the HDMP.

 

Featured People

Matthew Christopher, MD, PhD

Matthew Christopher, MD, PhD
Matthew Christopher, MD, PhD

Matt Christopher is Assistant Professor of Medicine at Washington University School of Medicine in St. Louis. He studies the genetic pathogenesis of acute myeloid leukemia and hopes to better elucidate the causes of chemotherapy resistance.

Christopher earned his MD and PhD from the Washington University School of Medicine in St. Louis and completed his residency and fellowship at Barnes-Jewish Hospital and the Washington University School of Medicine. He was awarded first prize in the Plenary Abstract Competition at the HDMP Annual Retreat in 2005 and 2017. In 2018, he was appointed Assistant Professor of Medicine.

Christopher was recently co-first author on the article Immune Escape of Relapsed AML Cells after Allogeneic Transplantation, published Oct. 31 in the New England Journal of Medicine. The study investigates changes in the expression of immune-regulatory genes in AML cells from patients who relapse after stem cell transplants. This discovery helps to explain how tumor cells can evolve in response to transplantation, evading the graft-versus-leukemia effect and leading to the recurrence of disease. In future, treatments could be devised to restore the graft-versus-leukemia effect by reversing these epigenetic changes. The senior author on the study is John DiPersio, MD.

Christopher’s work has also been published in Blood and the Journal of Experimental Medicine.

Meagan Jacoby, MD, PhD

Dr. Meagan Jacoby
Meagan Jacoby, MD, PhD

Meagan Jacoby is Assistant Professor of Medicine at Washington University School of Medicine in St. Louis. Her research focuses on myelodysplastic syndromes, acute myeloid leukemia, and genomics.

Jacoby received her MD and PhD from the Washington University School of Medicine and completed her residency at Barnes-Jewish Hospital and her fellowship at the Washington University School of Medicine. In 2015, she was named an American Society of Hematology Clinical Junior Faculty Scholar. Her work has appeared in JCI Insight, Blood, and Leukemia, and she was the co-first author of the article Mutation Clearance After Transplantation for Myelodysplastic Syndrome, recently published in the New England Journal of Medicine.

Mutation Clearance After Transplantation for Myelodysplastic Syndrome demonstrates that cancer-associated genetic mutations predict the recurrence of MDS in patients who have undergone stem cell transplants. Patients whose mutations were still present 30 days after transplantation were four times more likely to relapse than patients whose mutations had cleared. This finding could help physicians identify patients who require additional preventive care in order for their transplants to succeed.

Matthew Walter, MD

Dr. Matthew Walter
Matthew Walter, MD

Matthew Walter is Professor of Medicine at Washington University School of Medicine in St. Louis. His research seeks to identify and understand the genetic mutations that give rise to myelodysplastic syndromes and acute myeloid leukemia, with areas of concentration in spliceosome gene mutations, the clonal architecture of disease, and next-generation sequencing.

Walter earned his MD from the St. Louis University School of Medicine. He completed his residency at Johns Hopkins Hospital and his fellowship at Washington University Medical Center. He has received awards from the American Society of Hematology and the Leukemia and Lymphoma Society; in 2015, he was named to the American Society of Hematology Task Force on Precision Medicine. Since 2017, he has served as Scientific Director of the MDS Program at Washington University School of Medicine.

Walter was a senior author on Mutation Clearance After Transplantation for Myelodysplastic Syndrome.

Leukemia and MDS

Our research in leukemia and myelodysplastic syndromes (MDS) extends from bench to bedside, with ongoing basic, translational, and clinical studies. We have particular strengths in the use of genomics to dissect the pathogenesis and predict relapse for leukemia and MDS.  We are developing novel targeted therapies for leukemia and MDS based on our genomic studies.  We also are actively developing novel immunotherapies for leukemia, including a new type of natural killer cell immunotherapy and CAR-T cells that target T cell malignancies.

Basic science

Multiple laboratories in our group are studying basic mechanisms regulating normal and malignant hematopoiesis.  Major questions being addressed including the following: 1) mechanisms regulating hematopoietic stem cell function; 2) mechanisms by which mutations in epigenetic modifiers affect hematopoiesis; 3) the contribution of the bone marrow niche to malignant hematopoiesis; 4) the role of spliceosome and cohesin gene mutations in the development of myeloid malignancies.

Genomics

We are using state-of-the-art genomic techniques to interrogate leukemia and MDS.  These studies are being used to characterize mechanisms of disease pathogenesis and resistance to treatment.  For example, our recent study showed that a major mechanism of relapse following allogeneic hematopoietic cell transplantation for AML is downregulation of MCHII gene expression.  We also are using genomics to monitor response to induction chemotherapy in AML and using this information to determine best consolidation treatment.

Immunotherapies

We have a strong basic science program in cancer immunology to identify immunogenic neoantigens in cancer and define mechanisms of response and tolerance.  We have developed a new type of natural killer cell immunotherapy, which is being tested in clinical trials of patients with AML.  We are developing novel types of CAR-T cells that target T cell malignancies.

Stem cell transplantation

We have one of the largest hematopoietic stem cell transplantation programs in the country.  Several investigators are studying the hematopoietic niche to develop better methods of hematopoietic stem cell mobilization or ways to enhance stem cell engraftment.  We have active research programs studying graft versus host disease (GvHD).  For example, our group recently showed that baricitinib, a drug normally used as an arthritis drug, successfully blocked interferon gamma receptors and interleukin-6 receptors, eliminating GvHD in a mouse model.

 

 

Lymphoma

The lymphoma wing of the HDMP has a long history of excellence and a strong translational focus. Our laboratory research into lymphoma cell biology has given rise to new therapies and treatment protocols for patients. We have had recent success in immunotherapies, genomics, and drug trials. Through the study of novel drug regimens, we work to prevent or ameliorate patient relapse.

Novel therapies

We have a robust clinical trials program testing new drugs and new combinations of existing drugs. We’re studying brentuximab vedotin, ibrutinib, and lenalidomide, among others, and pursuing methods of risk-adapted treatment.

Genomics

We repeatedly turn to genomics in order to better understand lymphoma and to find superior solutions for our patients. Our researchers are conducting exome sequencing on follicular lymphoma and have tested mutations in large B cell lymphoma as a means of predicting patient outcomes. We’ve also investigated the genetic foundations of hepatosplenic T-cell lymphoma.

Immunotherapies

Our community is developing new immunotherapy solutions for lymphoma patients, including improved forms of CAR-T and Natural Killer cell therapies.

Minimal residual disease

We are seeking new ways to identify cancer cells that linger after treatment in T-cell lymphomas, including a T-cell receptor gene rearrangement assay and a cell free DNA (cfDNA) mutational profile.

 

Multiple Myeloma

The Myeloma Program at Washington University continues to grow in the breadth and depth in basic science, translational and clinical research. Our annotated tissue repository now has over 2000 clinically annotated patient samples. This has helped us advance numerous initiatives in genomics, imaging, personalized medicine, and immunotherapy.

Clinical care and trials

We have a dynamic, capacious clinical trials program and one of the largest bone marrow and stem cell transplantation programs in the country.  In 2017, we were the 2nd largest accrue for patients on clinical trials through the Multiple Myeloma Research Consortium (MMRC). Our MMRC transplant trial is now enrolling patients nationally at a dozen academic institutions. We hope to complete enrollment on this trial with over 200 patients in 2018. We were awarded the MMRF Collaborator Award at the American Society of Hematology Meeting in December 2017.

Healthcare outcomes research

Our researchers have been national leaders in determining the association of obesity with multiple myeloma and the possible protecting effects of metformin and statins in patients with plasma cell dyscrasias. Our program is also developing a national presence in geriatric oncology, with ongoing studies of frailty and geriatric assessment scales in elderly patients with myeloma. In addition, we are working to end disparities in cancer care by examining health care resource utilization in patients with multiple myeloma and its impact on the economics of care.

Genomics and personalized medicine

Researchers affiliated with our program are studying the germline DNA of over 1000 myeloma patients to discover genes conferring hereditary predisposition to multiple myeloma and cataloging the translocation events in the tumors of these patients and profiling drug-able genetic events using the CoMMpass database.

We have recently published on the creation of a Custom Capture Array and are now working on converting it from a research grade array to a CLIA certified diagnostic clinical tool. This invention has the potential to become a widely used test in the future.

We are also pioneering a novel 3D model which permits the study of multiple myeloma using a patient’s own primary cancer cells in their microenvironment.

Immunotherapy

Our program is involved in the creation of a variety of novel CAR-T constructs directed at BCMA and CS-1 for the treatment of myeloma. Researchers are also collaborating on a clinical trial that aims to study autologous Central Memory NK cells as a therapy for relapsed and refractory disease.

Clinical Trials

The members of the HDMP oversee a comprehensive clinical trials program that helps refine and redefine the standard of patient care. Active trials based in our institution include:

A phase 1/2 study of cytokine-induced memory-like NK cells in patients with AML or MDS

In this trial, our investigators are looking to identify the best dose and potential side effects of activated natural killer cells, a novel therapy for relapsed or refractory acute myeloid leukemia and myelodysplastic syndromes.  They propose that activated natural killer cells from a donor will prime the body’s immune system to fight cancer. The dosage of natural killer cells will be preceded by chemotherapy in a combined effort to eliminate cancer cells.

BL-8040 and Nelarabine for Relapsed or Refractory T-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

This trial is seeking to improve outcomes for relapsed or refractory adult patients with T-acute lymphoblastic leukemia and T-lymphoblastic lymphoma. Our investigators propose that adding BL-8040 to nelarabine will be a more effective salvage therapy for these patients than nelarabine on its own, with higher rates of complete remission and no additional toxicity. They surmise that this therapy may help prepare patients for allogeneic hematopoietic stem cell transplants, the only potentially curative treatment available to them.

Learn more about the clinical trials available to our patients for:

 

Newsworthy

Ley elected to National Academy of Sciences

Timothy J. Ley, MD, was recently elected to the National Academy of Sciences, one of the most prestigious honors that an American scientist can achieve. Ley, a member of the HDMP, spearheaded the effort to sequence the first cancer genome and has continued to conduct ground-breaking work on leukemia and cancer genomics.

CAR-T cell therapy making strides at School of Medicine

HDMP member John DiPersio, MD, PhD recently discussed his research into promising new forms of CAR-T cell therapy. DiPersio is working to create CAR-T cells from donor cells, which would expedite the treatment process. He also hopes to expand the application of CAR-T cell therapy to other forms of leukemia and lymphoma, as well as solid tumor cancers.

HDMP projects receive Siteman Investment Program grants

The Siteman Investment Program has awarded grants to projects sponsored by HDMP members John Welch, MD, PhD and Todd Fehniger, MD, PhD. Welch’s work will explore a combination of all-trans retinioic acid and bexarotene as a treatment for AML.  Fehniger is overseeing a number of projects aimed at translating basic lymphoma research into new therapies for patients.

Research on JARID2 appears in Cancer Cell

HDMP researchers have shown that deletion of the gene JARID2 furthers the development of secondary AML in patients with myelodysplastic syndromes or non-malignant myeloproliferative neoplasms. In a study published November 12 in Cancer Cell, they demonstrated that JARID2 is a hematopoietic tumor suppressor that could potentially be used to develop targeted therapies for patients with JARID2-deleted hematopoietic malignancies.

Study on tumor evolution in relapsed AML patients published in NEJM

Researchers affiliated with the HDMP have uncovered an epigenetic mechanism contributing to the relapse of AML following stem cell transplantation. In an article published October 31st in the New England Journal of Medicine, they demonstrated that epigenetic changes can depress the function of immune-regulatory genes, which allows certain AML cells to evade the graft-versus-leukemia effect and evolve in response to the transplant.

Leukemia SPORE renewed

The leukemia and MDS program has received another $11.5 million from the NIH in a renewal of their SPORE grant. Siteman is one of only three institutions nationwide to hold a SPORE, or “specialized program of research excellence,” in leukemia.

Multiple myeloma program receives $20 million gift

Paula C. and Rodger O. Riney have endowed the multiple myeloma research program with a $20 million donation. Their gift will establish the Paula C. and Rodger O. Riney Blood Cancer Research Initiative Fund, significantly advancing translational research in myeloma at Siteman Cancer Center.

Genetic testing predicts relapse in MDS patients

In a study published on September 13 in the New England Journal of Medicine, our researchers demonstrated that genetic analysis could help predict relapse in MDS patients treated with stem cell transplantation. Learn more here.