For more than 100 years, pathologists have recognized that cancer cells look different under a microscope. In fact, this is still how many cancers are diagnosed. Doctors use procedures, such as Pap tests, to look for enlarged nuclei in a patient’s cells – an indication that something might be wrong.
In blood cancers, like leukemia and myelodysplastic syndromes (MDS), this unusual cell morphology is known as Pelger-Huet Anomaly (PHA), a genetic disorder that is characterized by abnormally-shaped nuclei and chromatin. While PHA was first identified in 1928, it remains unclear how exactly the condition, which can be benign, is related to cancer.
That question is at the heart of a new study, published in the journal Cell Stem Cell, from the lab of ISCRM faculty member Sergei Doulatov, PhD, an Associate Professor of Medicine/Hematology. Doulatov and his team use induced pluripotent stem cells (iPSCs) to study how blood diseases impact stem cell biology. The lead author of the new paper is Andreea Reilly, a Postdoctoral fellow in the lab. Other authors include ISCRM faculty member Zhijun Duan and Janis L. Abkowitz, MD Head of the Division of Hematology.
“A lot of what we do is basic science, which is an important driver of translational discoveries,” says Doulatov. “What is really exciting in this study is the connection between cell morphology and cell function. Establishing a clearer connection between the hallmarks of PHA and certain blood cancers fills in a missing piece of the story and points to the field toward new diagnostic tools and therapies.”
According to the researchers, the crux of the connection between misshapen nuclei and blood cancers is a gene called lamin B1. Lamins are proteins that line the inside of the nucleus. Mutations in this gene are linked to certain inherited disorders, including progeria, a disease of accelerated aging.
