Paper Highlight: SciDAP Used in a Recent Study of B Cell Acute Leukemia published in Nature Communications

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Nayak, R.C., Chang, K.H., Singh, A.K. et al. Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis. Nat Commun 13, 3056 (2022). https://doi.org/10.1038/s41467-022-30651-7

In the last 10 years, the laboratory of Dr. Jose Cancelas Perez, MD, PhD, at Cincinnati Children’s Hospital has focused on the most frequent of the pediatric cancers, acute B-cell lymphoblastic leukemia. While the cure rates of this tumor have significantly improved in the last 40 years to reach ~90%, the remaining children who do not get cured represent a population as a large as pediatric AML or pediatric glioblastomas. This and the high toxicity of the existing therapies require further work towards understanding and identifying targets for intervention in B-ALL. Previously, Dr. Cancelas’s group identified the role of aPKC/Satb2 and Vav3 as novel genes controlling the epigenetic silencing of hotspot genes required for proliferation and differentiation arrest of B-cell progenitors/precursors. In this study, the Cancelas team collaborated with the Barski lab (also at Cincinnati Children’s Hospital) and Datirium to understand the mechanism of epigenetic gene silencing induced by Vav3.

Dr. Ramesh Nayak, PhD

We talked with Dr. Ramesh Nayak, PhD, the lead author of the manuscript.

What are the key findings of your study?

The progression of B-ALL has been extensively studied in the context of the acquisition of secondary mutations in B-cell proliferation and differentiation factors. Guanine nucleotide exchange factor Vav3 is required for leukemogenesis mediated by the oncogenic fusion protein BCR-ABL. However, the mechanisms of Vav3 action were not clear. In this study, we showed that Vav3 modulates the epigenetic landscape of transformed B-cell progenitors and progression of B-cell acute lymphoblastic leukemia (B-ALL) via Polycomb Repressive Complexes (PRC1 and PRC2). This study illustrates the epigenetic regulation of B-cell proliferation and differentiation factors during initiation and progression of B-ALL. This opens a new avenue to explore the mechanisms and to identify novel therapeutic targets.

What did you use SciDAP for?

The SciDAP bioinformatics platform was immensely helpful in analyzing our CUT&RUN datasets and generating publication quality images. We used it to map our CUT&RUN data, identify binding sites of PRC complex and genomic areas differentially bound by PRC members. Although I was very new in the field of epigenetics, with the help from SciDAP, I could analyze my samples, generate hypothesis, and publication quality images. Datirium team was very helpful in the data analyses and creating new pipelines as per the requirements of the project.

The full paper can be found at Nature Communications.