Researchers from Hamad Bin Khalifa University’s (HBKU) Qatar Computing Research Institute (QCRI), College of Health and Life Sciences (CHLS), and College of Science and Engineering (CSE) published the results of a joint research project with King’s College London in the 14th edition of prestigious multidisciplinary journal Nature Communications.

HBKU’s participants in this project were Dr. Halima Bensmail, Principal Scientist, QCRI, Dr. Borbala Mifsud, Assistant Professor, CHLS, and Abdurrahman Elbasir, recent PhD graduate, CSE, and Postdoc Research Fellow at The Wistar Institute. They worked with experts from King’s College London’s Department of Medical and Molecular Genetics and MRC - Asthma UK Centre in Allergic Mechanisms of Asthma to gain a more comprehensive understanding of the molecular mechanisms underlying the development and progression of Acute promyelocytic leukemia (APL). Specifically, they sought to characterize the PML::RARA fusion protein - the hallmark driver of APL -  which enables the uncontrolled production and accumulation of leukemia white blood cells.

To assist, the team used the integration of multi-omics datasets, developing a computational machine learning implementation called Regulatory Element Behavior Extraction Learning to deconvolute the complex, local transcription factor binding site environment at PML::RARA bound positions to reveal distinct signatures that modulate how PML::RARA directs the transcriptional response.

Their research determined that genes whose regulatory elements recruit the PML::RARA fusion protein do not always show uniform transcriptional repression, as is commonly believed. Instead, the PML::RARA fusion protein binding to regulatory elements did not always result in transcriptional repression, and that some genes were instead upregulated or unchanged in their expression levels. The project’s results suggested that the molecular mechanisms underlying APL may be more complex than previously thought, and that the role of PML::RARA in regulating gene expression may be more nuanced.