Search Results

Unfolding selective pathway dependencies of CALR mutated myeloproliferative neoplasms

The goal of this study is to selectively eradicate blood cancer cells carrying mutations in a gene called calreticulin. Genes and corresponding proteins required for cancer cell survival but not for the survival of healthy cells will first be targeted in mice, both genetically and by using drugs. Validated drugs will then be tested on patient samples. This study will lay the foundation to the development of tailored treatments for patients with calreticulin-mutated blood cancer.

Advancing New Therapeutic Strategies for Pediatric Acute Leukemias

Dr. Kimberly Stegmaier is performing pre-clinical research to identify promising therapeutic strategies for pediatric leukemia. Pediatric blood cancers comprise about 40% of all pediatric cancers. The most common pediatric blood cancer is acute lymphoblastic leukemia (ALL), which is curable in most patients through the use of chemotherapy. Though beneficial in the short term, destroying the cancer through chemotherapy often leads to long term health problems. For those that do not respond to chemotherapy, there are fewer therapeutic options.

Advancing the therapeutic landscape for Chronic Myelomonocytic Leukemia (CMML)

CMML is a universally lethal blood cancer characterized by increased monocytes (a type of white blood cell) in the peripheral blood and abnormal appearing cells within the bone marrow. Most CMML patients are clinically asymptomatic and remain so for weeks to months following diagnosis, with disease progression remaining inevitable. Despite therapeutic advances in similar blood cancers, no specific molecularly targeted therapies currently exist to treat CMML.

Predicting progression in myeloproliferative neoplasm patients by reconstructing the history of disease in each patient

Blood cancers called myeloproliferative neoplasms occur when one of the blood stem cells picks up a mutation. Some patients stay in the chronic phase of the disease for years whereas others rapidly progress with poor outcome. We recently measured when the cancer mutation first occurs and the rate of expansion of the cancer cells in individual patients. We will develop a method that uses the history of disease in each patient to identify those that are at risk of progression.

Genomic interrogation of high-risk myeloid neoplasms to identify new therapies

The long-term goal of my research program is to improve the outcomes for patients with high-risk myeloid blood cancers, particularly those with loss of chromosome 7 or CUX1. We are tackling this question using an arsenal of innovative methods and tools, including mouse models, human cells and patient samples, and state-of-the-art technologies to examine the cancer cell genome. Accomplishing this work will reveal new treatments and strategies for preventing blood cancers from arising.

Development of mutant GTPase-specific degraders for peripheral T cell lymphoma treatment

This project aims to develop targeted therapies against peripheral T cell lymphoma (PTCL), a diverse group of aggressive blood cancers with poor clinical outcomes. This project is tightly relevant to cancer control and treatment, promising to advance our understanding on how blood cancers initiate and progress, and lead to new therapeutics for the treatment of peripheral T cell lymphoma (PTCL). We will develop targeted therapeutics to engage an oncogenic RHOA GTPase mutant to treat PTCL and other types of tumors with similar genetic backgrounds.

CHEK2 as a predisposition gene for clonal hematopoiesis and hematopoietic malignancies

This proposal explores how inherited mutations in the DNA repair gene CHEK2 lead to blood cancers. Our work employs two unique resources: patient-derived cell lines and mice engineered with an inherited Chek2 variant that accurately models how bone marrow stem cells acquire DNA changes over time leading to bone marrow cancers. Our results may lead to new approaches that slow or prevent blood cancers in people with high risk.

Synergism of cell-intrinsic and cell-extrinsic factors in the clonal evolution of pre-malignant HSCs

We study the mechanisms of clonal hematopoiesis (CH), a process by which mutations provide hematopoietic stem cells (HSCs) with a fitness advantage. CH can precede the development of blood cancer. We use cutting-edge techniques to understand the effects of these mutations on HSC behavior. Our long-term goal is to identify ways to inhibit the growth of these mutant HSCs while sparing normal HSCs in people with CH. This may someday provide a blood cancer prevention method by eliminating the cells which carry the initial cancer-driving mutations.

Improving hematopoietic stem cell transplantation by defining novel regulators of engraftment

Blood-forming stem cells are routinely transplanted into patients to treat blood cancers. We discovered that multiple members of the GASP (G-protein coupled receptor Associated Sorting Proteins) family inhibit the function of blood-forming stem cells during transplantation. Our goal is to determine exactly how GASP family members inhibit these critical cells in order to inform our efforts to improve the efficiency of blood stem cell transplantation.

Patient Experience Research and Palliative Care Integration in Malignant Hematology

My research aims to improve the patient and caregiver experience of blood cancer care. To achieve this, I conduct trials of integrated palliative care interventions. Palliative care improves patient and caregiver outcomes for those with solid tumors, but less is known about its role in hematology. My research aims to design and implement integrated palliative care interventions in blood cancer settings, to improve the patient and caregiver experience of illness, regardless of treatment outcome.

Understanding sex differences in myeloid and dendritic differentiation and function to target high-risk leukemias including BPDCN

There are widely recognized but unexplained sex differences in cancer incidence and outcomes, including in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive leukemia that occurs over 3 times more frequently in men. We aim to identify male-female differences in plasmacytoid dendritic cells, the blood cell involved in BPDCN, to better understand this disease. Our goal is to use what we learn to improve the treatment of BPDCN and related blood cancers for both men and women.

Addressing Inequities in Access to Care for Patients with Hematologic Malignancy: Understanding the Impact of Telehealth Policies in Medicaid

Overcoming ibrutinib resistance in mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive blood cancer which affects about 3,000 individuals in the United States annually. Despite advances of novel therapies in blood cancers, MCL remains incurable, and patients ultimately succumb to disease. We seek to evaluate longitudinal samples from patients with MCL treated with novel therapies to understand the mechanisms of drug resistance. We identify novel targets, with a particular focus on protein turnover pathways, to overcome drug resistance and improve survival of patients with MCL.

Declaración sobre los estudios recientes de las vacunas contra la COVID-19 de tipo ARNm para pacientes con cáncer de la sangre

Modulating Signaling Pathways in Endothelial Cells to Abate Leukemic Progression

We seek to elucidate the mechanisms by which aging of the vascular system contributes to the decline in blood stem cell function and leads to diseases such as hematopoietic malignancies. We have developed novel model systems that have led to the discovery of rejuvenation factors that can restore the functional capacity of an aging blood and vascular system.

Randomized Trial of a Sexual Dysfunction Intervention for Hematopoietic Stem Cell Transplant Survivors

Our goal is to improve sexual function and quality of life for patients with blood cancers undergoing hematopoietic stem cell transplantation. We will conduct a clinical trial to evaluate whether a multi-component intervention to address sexual health and intimacy concerns can improve sexual function and satisfaction as well as quality of life and mood in hematopoietic stem cell transplant survivors. We will also explore whether improvement in sexual function leads to improvement in quality of life in this population.

Fertility and Pregnancy

In addition to our programs and services for blood cancer patients, families and caregivers, The Leukemia & Lymphoma Society (LLS) is pleased to offer an extensive directory of national and international resources. These organizations can help with cancer-related issues like financial assistance, support and counseling, assistance with transportation, and summer camps.

Targeting Enhancer Dysfunction in Hematological Malignancy

Blood cancers such as leukemia, lymphoma and myeloma may be caused by abnormal regulation of genes that control normal cell growth and development. Genes that are normally active can be silenced and/or genes normally not present in a blood cell are abnormally activated. The result can be an uncontrolled signal for continued cell growth or survival. Our group studies the molecular basis of this gene deregulation using cells cultured in the laboratory, human specimens, and animal models.

Targeting kinase-dependent dysregulation of transcription factor control in acute myeloid leukemia

Defining mechanisms of dysregulated gene control are central to understanding cancer and the development of effective therapies. Our research is focused on the mechanisms of gene control dysregulation in acute myeloid leukemia (AML), a refractory form of blood cancer that affects both children and adults. Using new methods for manipulating proteins, we are defining essential mechanisms by which AML cells enable cancer-causing gene expression. This work also allowed us to develop new drugs to specifically block this in cancer, but not healthy cells.