Northwestern Events Calendar

Feb
18
2016

BMG Seminar: Genetics and novel therapeutics for hematologic neoplasms - John Crispino, PhD

When: Thursday, February 18, 2016
9:00 AM - 10:00 AM CT

Where: Robert H Lurie Medical Research Center, Searle Seminar Room, 303 E. Superior, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Carson Nestler  

Group: Biochemistry & Molecular Genetics Seminar Series

Category: Lectures & Meetings

Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

John Crispino, PhD
Robert I. Lurie, MD and Lora S. Lurie Professor in Medicine-Hematology/Oncology and Biochemistry and Molecular Genetics
Northwestern University Feinberg School of Medicine

Children with Down syndrome (DS) develop both lymphoid and myeloid leukemia much more often than children without DS. With respect to the myeloid subtype, which predominantly involves excessive growth of immature megakaryocytes, we discovered that mutations in the hematopoietic transcription factor GATA1 are an initiating event, which cooperates with trisomy 21 to promote a transient pre-leukemia. A third genetic event, such as acquisition of mutations in signaling or epigenetic pathways, is needed for full transformation. We are currently investigating the identity of the specific genes on chromosome 21 that promote this leukemia and the mechanisms by which tertiary mutations contribute to disease progression. With respect to lymphoid leukemia, children with DS are 20 times more likely to develop B-cell acute lymphoblastic leukemia (DS-ALL). The genetics of this leukemia are complex, with as many as five events needed for transformation. We have recently demonstrated a key role for the chromosome 21 kinase DYRK1A in normal B-cell development and predict that its overexpression contributes to pathogenesis of DS-ALL. We are now studying the mechanisms by which DYRK1A facilitates transformation. I will present an update on the genetics of both of these subtypes of leukemia and will discuss our progress towards development of novel targeted therapies.

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