Centre for Cancer Research - Research Publications

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2020 - 2023 4
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Type: Journal Article × Author: Grimmond, Sean × Author: Blombery, Piers ×

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    Methyl-CpG binding domain 4, DNA glycosylase (MBD4)-associated neoplasia syndrome associated with a homozygous missense variant in MBD4: Expansion of an emerging phenotype
    Blombery, P ; Ryland, GL ; Fox, LC ; Stark, Z ; Wall, M ; Jarmolowicz, A ; Roesley, A ; Thompson, ER ; Grimmond, SM ; Panicker, S ; Kwok, F (WILEY, 2022-07)
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    Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia
    Kimura, S ; Montefiori, L ; Iacobucci, I ; Zhao, Y ; Gao, Q ; Paietta, EM ; Haferlach, C ; Laird, AD ; Mead, PE ; Gu, Z ; Stock, W ; Litzow, M ; Rowe, JM ; Luger, SM ; Hunger, SP ; Ryland, GL ; Schmidt, B ; Ekert, PG ; Oshlack, A ; Grimmond, SM ; Rehn, J ; Breen, J ; Yeung, D ; White, DL ; Aldoss, I ; Jabbour, EJ ; Pui, C-H ; Meggendorfer, M ; Walter, W ; Kern, W ; Haferlach, T ; Brady, S ; Zhang, J ; Roberts, KG ; Blombery, P ; Mullighan, CG (AMER SOC HEMATOLOGY, 2022-06-16)
    Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied. WGS was performed to detect mutations, structural variants, and copy number alterations. Integrated analysis of histone 3 lysine 27 acetylation and chromatin looping was performed using HiChIP. We identified a subset of 17 newly diagnosed and 5 relapsed B-ALL cases with a distinct gene expression profile and 2 universal and unique genomic alterations resulting from aberrant recombination-activating gene activation: a focal deletion downstream of PAN3 at 13q12.2 resulting in CDX2 deregulation by the PAN3 enhancer and a focal deletion of exons 18-21 of UBTF at 17q21.31 resulting in a chimeric fusion, UBTF::ATXN7L3. A subset of cases also had rearrangement and increased expression of the PAX5 gene, which is otherwise uncommon in B-ALL. Patients were more commonly female and young adult with median age 35 (range,12-70 years). The immunophenotype was characterized by CD10 negativity and immunoglobulin M positivity. Among 16 patients with known clinical response, 9 (56.3%) had high-risk features including relapse (n = 4) or minimal residual disease >1% at the end of remission induction (n = 5). CDX2-deregulated, UBTF::ATXN7L3 rearranged (CDX2/UBTF) B-ALL is a high-risk subtype of leukemia in young adults for which novel therapeutic approaches are required.
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    Description of a novel subtype of acute myeloid leukemia defined by recurrent CBFB insertions
    Ryland, GL ; Umeda, M ; Holmfeldt, L ; Lehmann, S ; Herlin, MK ; Ma, J ; Khanlari, M ; Rubnitz, JE ; Ries, RE ; Kosasih, HJ ; Ekert, PG ; Goh, HN ; Tiong, IS ; Grimmond, SM ; Haferlach, C ; Day, RB ; Ley, TJ ; Meshinchi, S ; Ma, X ; Blombery, P ; Klco, JM (AMER SOC HEMATOLOGY, 2023-02-16)
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    Inotuzumab ozogamicin resistance associated with a novel CD22 truncating mutation in a case of B-acute lymphoblastic leukaemia
    Ryland, GL ; Barraclough, A ; Fong, CY ; Fleming, S ; Bajel, A ; Hofmann, O ; Westerman, D ; Grimmond, S ; Blombery, P (WILEY, 2020-10)