Nora Heisterkamp Lab

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) develops in the bone marrow. At this location, contact with non-leukemia cells stimulates BCP-ALL cell growth and provides protection against anti-leukemia therapy. As there is ongoing communication between leukemia and non-leukemia cells, one overall goal is to further define these interactions in molecular terms, with an emphasis on glycosylation.

Glycosylation is a non-template-driven process regulated by enzymes that are exclusively dedicated to one or more biosynthetic pathways of the glycosylation machinery. Its importance is illustrated by the fact that around 2% of all human protein-encoding genes are reserved for this activity. Moreover, half of the more than 20,000 proteins encoded by the human genome are in fact glycoproteins that are modified by various types of sugar chains, the so-called glycans.

In the extracellular environment, the glycoprotein, proteoglycan and glycolipid components and their specific glyco-code are among the most important yet comparably least analyzed features. This is partly because glycosylation is a post-translational process of biomolecule modification that is strongly dependent on the cellular microenvironment and is not dependent upon a template.

Most immunotherapies and many targeted treatments are actually directed to cell surface and/or extracellular matrix glycoconjugates because all cells are covered by a dense layer of carbohydrate-containing cell surface molecules such as glycoproteins and glycolipids. In addition, glycosylation is intrinsically involved in controlling IgG-function beyond antigen recognition. This clearly makes the cellular microenvironment and its glycosylation a highly interesting, but still incompletely understood source of precision diagnostic biomarkers and therapeutic targets. Thus, the overall goal is to unravel the very complex glyco-code responsible for leukemia cell growth and survival in the bone marrow microenvironment.

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