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Role of HLX in leukemia induction and maintenance

We and others have shown how HLX overexpression keeps blood cells more immature by blocking their differentiation and promoting their proliferation, a characteristic which is inherent to AML. However, whether there is a causative role of HLX in the induction of AML is still unclear. Hence, the aim of my study is to better understand, using genetically engineered mice models, retroviral models, and human AML patient samples, how HLX drives AML at molecular level. This study will uncover potential therapeutic strategies for AML treatment in future.

Chronic Lymphocytic Leukemia 3D Model

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This model contains the following chapters. Click the "Interact in 3D" button to begin.

  • Healthy Bone Marrow
  • Normal Blood Cell Production
  • Proliferation of Cells and the Crowding Out of Normal Cells
  • Signs and Symptoms
 

Chronic Myeloid Leukemia 3D Model

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This model contains the following chapters. Click the "Interact in 3D" button to begin.

  • Healthy Bone Marrow
  • Normal Blood Cell Production
  • Proliferation of Cells and the Crowding Out of Normal Cells
  • Signs and Symptoms

Acute Myeloid Leukemia 3D Model

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This model contains the following chapters. Click the "Interact in 3D" button to begin.

  • Healthy Bone Marrow
  • Normal Blood Cell Production
  • Proliferation of Cells and the Crowding Out of Normal Cells
  • Signs and Symptoms

Understanding Leukemia in Children with Down Syndrome to Develop Better Therapies

This Specialized Center of Research is focused on identifying the contributions of chromosome 21, which is present in three copies in individuals with Down syndrome (DS), to acute leukemia. Children with DS are at a 20-fold increased risk of leukemia compared to the overall pediatric population and frequently have other health issues that complicate leukemia treatment.

Mechanisms of oncogenic transcription in NPM1-mutant myeloid leukemia

NPM1-mutated leukemia is the most common AML in adult and characterized by upregulations of HOXA/B genes and MEIS1. Given the importance of oncogenic transcriptional program, I will determine regulatory molecules that cooperate with mutant NPM1 on chromatin by combining CRISPR/Cas9 screening approach in an innovative model system of endogenous transcription reporters with proteomics approach. This will facilitate identification of novel therapeutic targets specific for NPM1-mutated AML.

Discovering the function and targeting dysregulated nuclear condensates in myeloid leukemia

Although molecular targeted therapy has dramatically changed how we treat cancer, the treatment for acute myeloid leukemia (AML) remains focused on the use of cytotoxic drugs with many patients eventually relapsing with their disease. Our studies have a uncovered a new nuclear structure that is dysregulated in myeloid leukemia. This proposal studies the identity and function of this nuclear body in human AML and strives to identify novel therapeutic strategies and targets in leukemia.
Myles, Reese, Aaron, and Lydia's images placed together in a collage

Moving Forward: 4 Young Blood Cancer Survivors Look Ahead

Blood cancer survivors have a unique path ahead of them—and that can feel challenging.  

Questions come up: Does treatment mean I have to pause everything? Do I tell my friends or coworkers (and how)? With my medical bills, how can I afford the education I want?  

New Targeted Therapies for Pediatric Acute Myeloid Leukemia

Our research focuses on the preclinical evaluation of new targeted therapies for high-risk subtypes of childhood AML. We are deploying screening approaches to delete each gene, one-by-one, to identify genes whose deletion leads to death of the leukemia cells. We will evaluate drugs developed against these targets in state-of-the-art models of pediatric AML. Our goal is to translate the most promising findings to clinical trials for children with these very poor outcome subsets of AML.

Targeting Leukemia Stem Cells with the Novel Antibody Drug Conjugate

To improve the cure rate of patients suffering from acute myeloid leukemia (AML), our study aims to target resistant leukemia stem cells by developing an 'antibody-drug conjugate' (ADC) against CD99, a protein expressed on these cells. Initial tests of two ADC versions have shown promise in combating AML. Our next steps involve refining the anti-CD99 antibody, identifying the optimal drug for conjugation, and testing the ADC on patient-derived leukemia models.

Molecular basis and new therapeutic strategies in lineage ambiguous leukemia

Lineage-ambiguous leukemias are high-risk blood cancers with unclear biologic basis and suboptimal treatment options. Here, I will identify the cell of origin of lineage ambiguous leukemia and investigate new therapeutic strategies through in vitro and in vivo experimental modeling approaches and preclinical drug studies in patient-derived xenografts. These studies will clarify the cellular and molecular alterations driving lineage ambiguity and advance a new, rational therapeutic approach.

Understanding the role of Metabolic Regulator SIRT5 in Acute Lymphoblastic Leukemia

SIRT5 is a master regulator of central energy metabolism. The survival and growth of Acute Myeloid Leukemia (AML) cells depend on SIRT5. I will employ genetic SIRT5 disruption and small molecule inhibitors to target SIRT5 in Acute Lymphoblastic Leukemia (ALL) cells and primary samples. This study aims to 1) determine the effects of SIRT5 inhibition on ALL in vitro and in vivo, and 2) identify SIRT5-regulated pathways and mechanisms underlying SIRT5 dependency in T-ALL.

Imatinib mesylate

Imatinib mesylate is FDA approved to treat

Cytarabine

Cytarabine is FDA approved to prevent and treat leukemia that has spread to the meninges (the three membranes that cover the brain and spinal cord). It is also FDA approved for use with other drugs to treat acute myeloid leukemia, acute lymphoblastic leukemia and chronic myeloid leukemia. This medicine may cause a temporary loss of hair in some people. After treatment with cytarabine has ended, normal hair growth should return.

Liposomal cytarabine (DepoCyt®) is given by intrathecal injection. It is FDA approved to treat lymphoma that has spread to the meninges.

Targeting AML

 

Not for lack of trying, we’ve seen very little progress over the past 40 years in treating acute myeloid leukemia (AML), an aggressive and deadly blood cancer. But we’re finally starting to see the needle move and The Leukemia & Lymphoma Society (LLS) is playing a leading role in going on the offensive against the disease.

Blinatumomab

Blinatumomab is FDA approved for the treatment of adult and pediatric patients one month and older with: 

Strategic combinations to overcome therapeutic resistance and relapse in acute myeloid leukemia

Acute myeloid leukemia (AML) is the most fatal type of leukemia and has a high rate of relapse following current therapies. We have recently uncovered that RSPO3-LGR4 pathway is a key regulator of leukemia-initiating cell activity and is exclusively activated in relapsed and refractory AML. Our project aims to investigate the mechanistic link between the pathway activation and therapy resistance, and design combination therapies that would overcome resistance and improve the treatment of relapsed leukemia.

Diagnosed with a Blood Cancer? Important Questions You Might Not Think to Ask

What is my actual diagnosis? Find out your exact diagnosis. Ask your doctor to write down the exact name of your sub-type and take the paper with you. For example, knowing you have “a B-cell lymphoma” isn’t good enough. Follicular and diffuse large B-cell are both B-cell lymphomas but with very different prognoses and treatment plans. Leukemia also has different sub-types. Knowing your specific sub-type helps you understand what disease you are dealing with, how aggressive it is, and what to expect from treatment.