Armed with New Grants, Sylvester Researcher Hopes to Develop Leukemia Therapies

Lan Wang, Ph.D., assistant professor of biochemistry and molecular biology, has received three grants this year for her research studies in the field of blood cancers.

“My research focuses on understanding the pathogenesis of hematological malignancies and stem cell studies,” said Wang. “In particular, I am interested in identifying the genes that are disrupted and developing new therapeutic strategies for patients with these diseases.”

In June, she was awarded two grants:

• $12,500 by the Gabrielle’s Angel Foundation for Cancer Research for “Targeting Inhibitor of DNA Binding 1 in Hematological Malignancies.”

• $50,000 by the Women’s Cancer Association of the University of Miami for “Targeting Self-Renewal in MLL-AF9-Driven Leukemia.”

In July, she was awarded an additional grant:

• $100,000 by the Leukemia Research Foundation for “Targeting the Abnormal Transcription Regulators in Leukemia.”

Leukemic stem cells can initiate and maintain acute myelogenous leukemia (AML), a cancer that starts inside the bone marrow, Wang explained. Leukemic stem cells share one important characteristic with normal hematopoietic stem cells, namely the ability to self-renew. Unlike normal hematopoietic stem cells, however, AML cells are blocked in their ability to differentiate. Instead, they are locked in an immature state in which they don’t undergo normal apoptosis, or programmed cell death.

AML is commonly associated with aberrant transcriptional regulation, which can initiate or promote the development of leukemic stem cells. High levels of Id1, a dominant inhibitor of basic-HLH transcription factors, is a poor prognosis for AML patients who are treated solely with conventional chemotherapy.

“We recently showed that Id1 is upregulated by AML1-ETO and is required for hematopoietic stem cell self-renewal,” said Wang. “We propose to study the relevance of Id1 in the self-renewal and maintenance of leukemic stem cells by the AML1-ETO9a and MLL-AF9 fusion proteins, to determine whether Id1 could be a useful target for attacking leukemic stem cells.

“Specifically, we plan to identify the effect of Id1 on leukemic hematopoiesis using mouse models. Our prediction is that blocking Id1 will inhibit the formation or propagation of leukemic stem cells. The information generated by this study will be useful for developing targeted therapeutics for AML.”

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