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Gregg

The date was May 15, 2015, in the local office of the hematologist/oncologist and I was given this message after the results of my bone marrow biopsy taken a week earlier. 

Exploiting Vulnerabilities in RNA Splicing to Treat Hematologic Malignancies

RNA splicing is a central metabolic pathway that is frequently perturbed in hematopoietic malignancies (HMs) that harbor mutations in spliceosome components (most commonly affecting SRSF2, SF3B1, U2AF1, or ZRSR2). These mutations are particularly prevalent in myeloid malignancies (e.g., MDS, MDS/MPN, sAML), but recent pan-cancer studies have implicated aberrant splicing in >30 tumor types.

Dissecting the mitochondrial alterations by aberrant NPM1 to the pathogenesis of myelodysplastic syndrome

Survival rates for those afflicted with MDS have not improved despite extensive effort to identify the key genetic events in its pathogenesis. This project elucidates the contributions of aberrant NPM1 to hematological disorders, with a focus on mitochondrial fitness and inflammasome activation. The resulting insights into the metabolic, genetic and proteomic requirements of homeostasis that are critical to preventing aging will have a major impact on the treatment of hematological malignancies.

Targeting Epigenetics in Myeloid Malignancies

We have a highly collaborative team of investigators, whose goal is to develop novel therapeutic approaches to MDS and AML as well as to improve current therapies for these diseases based on a detailed understanding of how epigenetic dysregulation contributes to myeloid neoplasia. We are focusing on the clonal MDS or AML cell and on the bone marrow microenvironment (BMME), including immune cells that could contribute to or limit the progression of these disorders.

Reduced-Intensity Allogeneic Stem Cell Transplantation

Reduced-intensity allogeneic stem cell transplantation (sometimes called mini-transplant or nonmyeloablative transplant), like a standard allogeneic stem cell transplantation, uses stem cells from a donor, but the conditioning treatment contains lower, less toxic doses of chemotherapy and radiation. This type of SCT may be an option for certain patients who are older or who are otherwise not healthy enough or strong enough to undergo standard allogeneic SCT.

Targeting TP53-Y220C mutant AML

TP53-Y220C is a recurrent hotspot TP53 mutation observed predominantly in AML and MDS among hematological malignancies. This study aims to investigate the mechanism of action and therapeutic activity of PC14586, a compound designed to bind p53-Y220C protein and stabilize it in the wild-type conformation and to develop mechanism-based combinations that improve its efficacy in TP53-Y220C mutant AML.

Targeting Myeloid Malignancies through IRAK4 Synthetic Lethality Dependencies

Based on our preliminary data, we hypothesize that IRAK4 inhibition leads to LSPC reprogramming in MDS and AML. Aim 1 will evaluate the mechanism by which IRAK4 inhibition leads to LSPC reprogramming in cell lines, mice, and PDX samples. Aim 2 will concentrate on understanding of how IRAK4 inhibition creates synthetic lethal dependencies with the CELMoD CC-885 and how neosubstrates of CC-885 mediate the synergy upon IRAK4 inhibition in leukemic cells.

Imatinib mesylate

Generic name Imatinib mesylate Pronunciation  i-MAT-i-nib MES-i-late Brand name(s), other common name(s) Gleevec® Drug type   Tyrosine kinase inhibitor How the drug is given By mouth Indications and Usage

Imatinib mesylate is FDA approved to treat

Steven

My name is Steve. My purpose is to give others hope and the possibility of tomorrows. I am a leukemia survivor, specifically myelodysplastic syndrome (MDS). Today, one year after my bone marrow transplant, I am 100% cancer-free!

Disease Complications

In medicine, a complication is a medical problem that occurs during the course of a disease or after a procedure or treatment. Possible complications of PV include:

Treatment

It's important that your doctor is experienced in treating patients with acute myeloid leukemia (AML) or has access to an AML specialist.

Types of AML Treatment

Doctors use several types of treatment for adults with AML, some at different stages. Click on the links below to read more about each type of treatment.

Complications of CLL or CLL Treatment

Infection

People with CLL are more likely to get infections.  

Disease- and Treatment-Related Pain

People with cancer can have pain caused by the cancer itself, its treatment, or both. They may also have pain caused by other health problems that are unrelated to cancer (like arthritis or diabetes).

Increased pain does not mean that the cancer is getting worse, but you should always tell your healthcare team if you have increased pain.

It’s important to remember that no matter what the cause, pain can be treated.

The hills I have climbed

Side Effects

Cancer therapy for non-Hodgkin lymphoma (NHL) can sometimes produce side effects. For most patients, treatment side effects are temporary and go away once therapy ends. For other patients, side effects can be more severe, sometimes requiring hospitalization. Some patients never have side effects.

Before you undergo treatment, talk with your doctor about potential side effects. In recent years, new drugs and other therapies have increased the ability to control side effects.