Bilineal evolution of a U2AF1-mutated clone associated with acquisition of distinct secondary mutations. Montgomery, N. D, Galeotti, J., Johnson, S. M., Commander, L., Weimer, E. T., Chandra, P. K., Nazir, T., Alexander, T. B., Zeidner, J. F., & Foster, M. C Blood Advances, October, 2021.
Bilineal evolution of a U2AF1-mutated clone associated with acquisition of distinct secondary mutations [link]Paper  doi  abstract   bibtex   6 downloads  
Rare hematologic malignancies display evidence of both myeloid and lymphoid differentiation. Here, we describe such a novel bilineal event discovered in an adult woman with B-lymphoblastic leukemia (BLL). At the time of BLL diagnosis, the patient had a normal karyotype and a bulk sequencing panel identified pathogenic variants in BCOR, EZH2, RUNX1, and U2AF1, a genotype more typical of myeloid neoplasia. Additionally, the patient was noted to have 3-year history of cytopenias, and morphologic dyspoiesis was noted on post-treatment samples, raising the possibility of an antecedent hematologic disorder. To investigate the clonal architecture of her disease, we performed targeted sequencing on fractionated samples enriched for either B-lymphoblasts or circulating granulocytes. These studies revealed a truncal founder mutation in the spliceosome gene U2AF1 in both fractions, while distinct secondary mutations were present only in B-lymphoblasts (BCOR, NRAS) or myeloid cells (ASXL1, EZH2, RUNX1). These results indicate that both processes evolved from a common U2AF1-mutated precursor, which then acquired additional mutations during a process of divergent evolution and bilineal differentiation. Our findings highlight novel mechanisms in BLL leukemogenesis and expand the spectrum of observed bilineal neoplasms.
@article{montgomery_bilineal_2021,
	title = {Bilineal evolution of a {U2AF1}-mutated clone associated with acquisition of distinct secondary mutations},
	issn = {2473-9529},
	url = {https://doi.org/10.1182/bloodadvances.2021005308},
	doi = {10.1182/bloodadvances.2021005308},
	abstract = {Rare hematologic malignancies display evidence of both myeloid and lymphoid differentiation. Here, we describe such a novel bilineal event discovered in an adult woman with B-lymphoblastic leukemia (BLL). At the time of BLL diagnosis, the patient had a normal karyotype and a bulk sequencing panel identified pathogenic variants in BCOR, EZH2, RUNX1, and U2AF1, a genotype more typical of myeloid neoplasia. Additionally, the patient was noted to have 3-year history of cytopenias, and morphologic dyspoiesis was noted on post-treatment samples, raising the possibility of an antecedent hematologic disorder. To investigate the clonal architecture of her disease, we performed targeted sequencing on fractionated samples enriched for either B-lymphoblasts or circulating granulocytes. These studies revealed a truncal founder mutation in the spliceosome gene U2AF1 in both fractions, while distinct secondary mutations were present only in B-lymphoblasts (BCOR, NRAS) or myeloid cells (ASXL1, EZH2, RUNX1). These results indicate that both processes evolved from a common U2AF1-mutated precursor, which then acquired additional mutations during a process of divergent evolution and bilineal differentiation. Our findings highlight novel mechanisms in BLL leukemogenesis and expand the spectrum of observed bilineal neoplasms.},
	number = {bloodadvances.2021005308},
	urldate = {2021-10-05},
	journal = {Blood Advances},
	author = {Montgomery, Nathan D and Galeotti, Jonathan and Johnson, Steven M. and Commander, Leah and Weimer, Eric T. and Chandra, Pranil K. and Nazir, Tariq and Alexander, Thomas B. and Zeidner, Joshua F. and Foster, Matthew C},
	month = oct,
	year = {2021},
	keywords = {Custom, Custom Panel},
}
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