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. 2023 Apr;62(4):202-209.
doi: 10.1002/gcc.23110. Epub 2022 Dec 7.

UBTF-internal tandem duplication as a novel poor prognostic factor in pediatric acute myeloid leukemia

Taeko Kaburagi  1   2 , Norio Shiba  3 , Genki Yamato  1   2 , Kenichi Yoshida  4 , Ken Tabuchi  5 , Kentaro Ohki  6 , Etsuko Ishikita  1   2 , Yusuke Hara  2 , Yuichi Shiraishi  7 , Hirohide Kawasaki  1 , Manabu Sotomatsu  1 , Takumi Takizawa  2 , Tomohiko Taki  8 , Nobutaka Kiyokawa  6 , Daisuke Tomizawa  9 , Keizo Horibe  10 , Satoru Miyano  11 , Takashi Taga  12 , Souichi Adachi  13 , Seishi Ogawa  4   14   15 , Yasuhide Hayashi  1   16
Affiliations

UBTF-internal tandem duplication as a novel poor prognostic factor in pediatric acute myeloid leukemia

Taeko Kaburagi et al. Genes Chromosomes Cancer. 2023 Apr.

Abstract

The prognosis of pediatric acute myeloid leukemia (AML) has improved via stratification therapy. However, relapse or death occurs in 30%-40% of cases. Novel genetic factors for pediatric AML need to be elucidated to improve prognosis. We detected recurrent internal tandem duplication in upstream binding transcription factor (UBTF-ITD) in 1.2% (6/503) of Japanese pediatric patients with de novo AML. No UBTF-ITD was detected in 175 adult patients with AML or in 65 cell lines that included 15 AML, 39 acute lymphoblastic leukemia, five chronic myeloid leukemia, and six neuroblastoma cell lines. All UBTF-ITDs were found in exon 13 and shared a duplicated region. UBTF-ITD was more frequently detected in patients with trisomy 8, FLT3-ITD, WT1 mutation, and/or high PRDM16 expression (trisomy 8, 3/6; FLT3-ITD, 5/6; WT1 mutation, 2/6; and high PRDM16 expression, 6/6). Gene expression patterns of patients with UBTF-ITD were similar to those of patients with NUP98::NSD1 or FUS::ERG. Survival analysis of the AML-05 cohort revealed that patients with UBTF-ITD had worse outcomes than those without UBTF-ITD (3-year event-free survival, 20% vs. 55%; 3-year overall survival, 40% vs. 74%). Moreover, among the 27 patients with trisomy 8, all three patients with UBTF -ITD had a poor prognosis resulting in early events (relapse or non-complete remission) within 1 year. Our findings suggest that UBTF-ITD may be a novel and significant prognostic factor for pediatric patients with AML.

Keywords: AML; FLT3-ITD; PRDM16; UBTF-ITD; pediatric; trisomy 8.

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References

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