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The genomic landscape of hypodiploid acute lymphoblastic leukemia
Open accessAbstract
The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24–31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32–39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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Zhang, J., Walsh, M. F., Wu, G., Edmonson, M. N., Gruber, T. A., Easton, J., Hedges, D., Ma, X., Zhou, X., Yergeau, D. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1508054 · Cited by 1,345
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Metadata
- Authors
- Holmfeldt, L., Wei, L., Diaz-Flores, E., Walsh, M., Zhang, J., Ding, L., Payne-Turner, D., Churchman, M., Andersson, A., Chen, S.-C., McCastlain, K., Becksfort, J., Ma, J., Wu, G., Patel, S. N., Heatley, S. L., Phillips, L. A., Song, G., Easton, J., Parker, M., Chen, X., Rusch, M., Boggs, K., Vadodaria, B., Hedlund, E., Drenberg, C., Baker, S., Pei, D., Cheng, C., Huether, R., Lu, C., Fulton, R. S., Fulton, L. L., Tabib, Y., Dooling, D. J., Ochoa, K., Minden, M., Lewis, I. D., To, L. B., Marlton, P., Roberts, A. W., Raca, G., Stock, W., Neale, G., Drexler, H. G., Dickins, R. A., Ellison, D. W., Shurtleff, S. A., Pui, C.-H., Ribeiro, R. C., Devidas, M., Carroll, A. J., Heerema, N. A., Wood, B., Borowitz, M. J., Gastier-Foster, J. M., Raimondi, S. C., Mardis, E. R., Wilson, R. K., Downing, J. R., Hunger, S. P., Loh, M. L., & Mullighan, C. G.
- Venue
- Nature Genetics
- Published
- 2013-01-20
- Volume
- 45
- Issue
- 3
- Pages
- 242-252
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2063662864
- Cited by
- 731
- References
- 20
- FWCI
- 63.66
- Type
- journal article
- Language
- en
- Open access
- green
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- Holmfeldt, L., Wei, L., Diaz-Flores, E., Walsh, M., Zhang, J., Ding, L., Payne-Turner, D., Churchman, M., Andersson, A., Chen, S.-C., McCastlain, K., Becksfort, J., Ma, J., Wu, G., Patel, S. N., Heatley, S. L., Phillips, L. A., Song, G., Easton, J., . . . Mullighan, C. G. (2013). The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nature Genetics. https://doi.org/10.1038/ng.2532
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