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Title: Fusion partner–specific mutation profiles and KRAS mutations as adverse prognostic factors in MLL-rearranged AML
Authors: Matsuo, Hidemasa  kyouindb  KAKEN_id  orcid (unconfirmed)
Yoshida, Kenichi
Nakatani, Kana
Harata, Yutarou
Higashitani, Moe
Ito, Yuri
Kamikubo, Yasuhiko
Shiozawa, Yusuke
Shiraishi, Yuichi
Chiba, Kenichi
Tanaka, Hiroko
Okada, Ai
Nannya, Yasuhito
Takeda, June
Ueno, Hiroo
Kiyokawa, Nobutaka
Tomizawa, Daisuke
Taga, Takashi
Tawa, Akio
Miyano, Satoru
Meggendorfer, Manja
Haferlach, Claudia
Ogawa, Seishi
Adachi, Souichi
Author's alias: 松尾, 英将
吉田, 健一
中谷, 香菜
原田, 優太郎
東谷, 萌絵
伊東, 優里
上久保, 靖彦
塩澤, 裕介
白石, 友一
千葉, 健一
田中, 洋子
岡田, 愛
南谷, 泰仁
竹田, 淳恵
上野, 浩生
清河, 信敬
富澤, 大輔
多賀, 崇
多和, 昭雄
宮野, 悟
小川, 誠司
足立, 壯一
Issue Date: 13-Oct-2020
Publisher: American Society of Hematology
Journal title: Blood Advances
Volume: 4
Issue: 19
Start page: 4623
End page: 4631
Abstract: Mixed-lineage leukemia (MLL) gene rearrangements are among the most frequent chromosomal abnormalities in acute myeloid leukemia (AML). MLL fusion patterns are associated with the patient’s prognosis; however, their relationship with driver mutations is unclear. We conducted sequence analyses of 338 genes in pediatric patients with MLL-rearranged (MLL-r) AML (n = 56; JPLSG AML-05 study) alongside data from the TARGET study’s pediatric cohorts with MLL-r AML (n = 104), non–MLL-r AML (n = 581), and adult MLL-r AML (n = 81). KRAS mutations were most frequent in pediatric patients with high-risk MLL fusions (MLL-MLLLT10, MLL-MLLT4, and MLL-MLLT1). Pediatric patients with MLL-r AML (n = 160) and a KRAS mutation (KRAS-MT) had a significantly worse prognosis than those without a KRAS mutation (KRAS-WT) (5-year event-free survival [EFS]: 51.8% vs 18.3%, P < .0001; 5-year overall survival [OS]: 67.3% vs 44.3%, P = .003). The adverse prognostic impact of KRAS mutations was confirmed in adult MLL-r AML. KRAS mutations were associated with adverse prognoses in pediatric patients with both high-risk (MLLT10+MLLT4+MLLT1; n = 60) and intermediate-to-low–risk (MLLT3+ELL+others; n = 100) MLL fusions. The prognosis did not differ significantly between patients with non–MLL-r AML with KRAS-WT or KRAS-MT. Multivariate analysis showed the presence of a KRAS mutation to be an independent prognostic factor for EFS (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.35-3.59; P = .002) and OS (HR, 1.85; 95% CI, 1.01-3.31; P = .045) in MLL-r AML. The mutation is a distinct adverse prognostic factor in MLL-r AML, regardless of risk subgroup, and is potentially useful for accurate treatment stratification. This trial was registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry (UMIN-CTR; as #UMIN000000511.
Description: 急性骨髄性白血病の予後を予測する新規マーカーを発見 --リスクに応じた適切な治療につながる可能性--. 京都大学プレスリリース. 2020-10-02.
DOI(Published Version): 10.1182/bloodadvances.2020002457
PubMed ID: 32991719
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