Hematology Branch

Investigators in the Hematology Branch (HB) study normal and abnormal hematopoiesis—the development and differentiation of stem cells into multiple types of blood cells—in the clinic and in the research laboratory. Patients who have a variety of bone marrow failure syndromes and acute and chronic leukemias attend the HB’s clinic and may be enrolled in clinical research protocols at the NIH Clinical Center. Interventions are intended to reverse marrow failure, cure or ameliorate leukemias by stem cell transplant, and control lymphoproliferative diseases such as chronic lymphocytic leukemia by drug therapy. In the laboratory, basic cellular and molecular biology, immunologic, and genomic techniques and approaches are used to study patient samples, cells, cell lines, and in animal models. The Branch has been an international leader in developing understanding of the pathophysiology of hematologic diseases and improving their outcomes.

Our Labs

Hematopoiesis and Bone Marrow Failure

Research in the Hematopoiesis and Bone Marrow Failure Laboratory, led by Dr. Neal Young, spans the basic sciences, clinical trials, and epidemiology. Bench work involves methods of cell and molecular biology, immunology, and virology. Blood cell production in healthy individuals and especially in patients with bone marrow failure is the main theme. Advanced techniques most recently include single cell RNAseq, CRISPR-Cas9 gene editing, multicolored bar coded flow cytometry, and SomaLogic deep proteomics.

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Lymphoid Malignancies

The Laboratory of Lymphoid Malignancies, led by Dr. Adrian Wiestner, aims to improve the treatment of patients with chronic lymphocytic leukemia (CLL). The group combines clinical and laboratory investigations to identify the molecular drivers of the disease. These insights are translated into clinical trials that seek to selectively eliminate tumor cells using targeted therapy. CLL samples donated by patients participating in these clinical trials are in turn used in the laboratory to study the effectiveness of the treatment and the reaction of the tumor cells to drugs, which can provide insights how to further improve the therapy.

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Myeloid Malignancies

While considerable therapeutic advances using targeted therapies have been made for many malignancies, the most common treatment for acute myeloid leukemia (AML) has not changed in nearly 40 years. Although the majority of patients treated with chemotherapy will achieve an initial remission, subsequent treatment with either further chemotherapy or allogeneic stem cell transplantation (SCT) is effective at preventing leukemic relapse in only about half of these individuals. The outlook is often especially suboptimal for those diagnosed with AML but not eligible for this intensive therapy due to advanced age or medical co-morbidity. Despite the lack of progress with conventional treatments, recent advances in the scientific understanding of the genetic diversity of AML, new developments in immunotherapy and the powerful graft-versus-leukemia effect already observed after SCT all offer hope that AML is potentially susceptible to control by the immune system in the non-SCT setting. Research in the Laboratory of Myeloid Malignancies, led by Dr. Christopher Hourigan, focuses on three complementary approaches that are united by an overriding theme of performing translational human immunology research in order to find ways to detect, prevent and treat AML relapse.

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Regenerative Therapies for Inherited Blood Disorders

Gene and stem cell-based regenerative therapies hold the promise of replacing lost, damaged, or aging cells and tissues in the human body. Despite substantial strides in understanding stem cell biology in humans, major challenges have slowed the translation this knowledge into medical therapies. The Laboratory of Regenerative Therapies for Inherited Blood Disorders, led by Dr. Andre Larochelle, is investigating novel strategies and stem cell concepts that can help advance the translational regenerative field, with a focus on inherited disorders affecting blood-forming hematopoietic stem cells (HSCs). Dr. Larochelle’s program aims to develop regenerative therapies for inherited HSC disorders by: 1) CRISPR-Cas9 and retroviral mediated-genetic correction of HSCs for clinical applications; 2) derivation of engraftable HSCs from genetically corrected induced pluripotent stem cells (iPSCs); and 3) in vivo and ex vivo expansion of HSCs.

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Stem Cell Allogeneic Transplantation

The Stem Cell Allogeneic Transplantation Laboratory, led by Dr. John Barrett, has carried out clinical trials in stem cell transplantation (SCT) as a treatment for leukemia for over 23 years at NIH. His current research in SCT focuses on improving transplant outcome through immune manipulations using cell therapy and lymphocyte growth factors. Stem cell transplantation offers the chance of cure for leukemia patients through a unique graft-versus-leukemia (GVL) effect conferred by an immune reaction of the donor graft against the patient’s leukemia. Unfortunately, the GVL reaction often develops alongside an unwanted and potentially fatal graft-versus host disease (GVHD). GVHD can be controlled through reducing the immunity of the graft. While transplants for leukemia can now be performed with considerable safety, fatal viral infections and disease relapse still reduce the success of SCT as a treatment for leukemia.

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