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1.	Marincevic-Zuniga, Y, et al. (author) Molecular classification of B-other pediatric B-cell precursor acute lymphoblastic leukemia by DNA methylation and RNA-sequencing 2019 In: EUROPEAN JOURNAL OF HUMAN GENETICS. - 1018-4813. ; 27, s. 1106-1107 Conference paper (other academic/artistic)
2.	Ofverholm, I. Ivanov, et al. (author) Prognostic Impact of IKZF1 Deletions in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia Treated According to Nopho Protocols - the Swedish Experience 2014 In: Haematologica. - 0390-6078 .- 1592-8721. ; 99:S1, s. 9-9 Journal article (other academic/artistic)
3.	Orgueira, AM, et al. (author) Epigenetic Profiling and Machine Learning for Enhanced Risk Stratification in Pediatric Acute Lymphoblastic Leukemia 2023 In: BLOOD. - 0006-4971. ; 142 Conference paper (other academic/artistic)
4.	Pilheden, M., et al. (author) Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia 2022 In: Hemasphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 6:10 Journal article (peer-reviewed)abstract Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3(D835H) or NRAS(G13D/G12S) mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.

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Type of publication: conference paper (2); journal article (2)

Type of content: other academic/artistic (3); peer-reviewed (1)

Author/Editor: Noren-Nystrom, U (4); Heyman, M. (3); Barbany, G (2); Schmiegelow, K. (2); Lonnerholm, G (2); Nordlund, J. (2); show more...; Johansson, B (1); Nordgren, A (1); Ma, J (1); Lausen, B (1); Nilsson, S. (1); Ahlgren, L (1); Pilheden, M (1); Sturesson, H (1); Walsh, M (1); Castor, A (1); Lohi, O (1); Zachariadis, V (1); Fogelstrand, Linda, ... (1); Nordlund, Jessica (1); Lilljebjorn, H. (1); Fioretos, T. (1); Chen, Y. L. (1); Pronk, C. J. (1); Olsson, L (1); Flaegstad, T (1); Forestier, E (1); Zhang, J. H. (1); Golovleva, I (1); Sinnett, D (1); Sjogren, H. (1); Krali, O (1); Kanerva, J (1); Marincevic-Zuniga, Y (1); Nystedt, S (1); Almlof, J (1); Ofverholm, I. Ivanov (1); Orgueira, AM (1); Raindo, AP (1); Arias, JAD (1); Perez, MSG (1); Encinas, MP (1); Sanmartin, MF (1); Vence, NA (1); Hyrenius-Wittsten, A ... (1); Gonzalez-Pena, V. (1); Marquart, H. V. H. (1); Tamm, K. P. (1); Asklin, J. (1); Song, G. C. (1); show less...

University: Karolinska Institutet (3); University of Gothenburg (1); Uppsala University (1)

Language: English (4)

Research subject (UKÄ/SCB): Medical and Health Sciences (2)

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