Significance of FLT3-tyrosine kinase domain mutation as a prognostic factor for acute myeloid leukemia

被引：20

作者：

Sakaguchi, Masahiro ^{[1
]}

Yamaguchi, Hiroki ^{[1
]}

Kuboyama, Marika ^{[1
]}

Najima, Yuho ^{[2
]}

Usuki, Kensuke ^{[3
]}

Ueki, Toshimitsu ^{[4
]}

Oh, Iekuni ^{[5
]}

Mori, Shinichiro ^{[6
]}

Kawata, Eri ^{[7
,15
]}

Uoshima, Nobuhiko ^{[7
]}

Kobayashi, Yutaka ^{[7
]}

Kako, Shinichi ^{[8
]}

Tajika, Kenji ^{[9
]}

Shono, Katsuhiro ^{[10
]}

Kayamori, Kensuke ^{[11
]}

Hagihara, Masao ^{[12
]}

Kanda, Junya ^{[13
]}

Uchiyama, Hitoji ^{[14
]}

Kuroda, Junya ^{[15
]}

Uchida, Naoyuki ^{[16
]}

Kubota, Yasushi ^{[17
]}

Kimura, Shinya ^{[17
]}

Kurosawa, Saiko ^{[18
]}

Date, Kenta ^{[1
]}

Nakajima, Nana ^{[1
]}

Marumo, Atsushi ^{[1
]}

Omori, Ikuko ^{[1
]}

Fujiwara, Yusuke ^{[1
]}

Terada, Kazuki ^{[1
]}

Yui, Shunsuke ^{[1
]}

Wakita, Satoshi ^{[1
]}

Arai, Kunihito ^{[1
]}

Kitano, Tomoaki ^{[1
]}

Kakihana, Kazuhiko ^{[2
]}

Kanda, Yoshinobu ^{[5
,8
]}

Ohashi, Kazuteru ^{[2
]}

Fukuda, Takahiro ^{[18
]}

Inokuchi, Koiti ^{[1
]}

机构：

[1] Nippon Med Sch, Dept Hematol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138603, Japan

[2] Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Hematol Div, Tokyo, Japan

[3] NTT Med Ctr Tokyo, Dept Hematol, Tokyo, Japan

[4] Nagano Red Cross Hosp, Dept Hematol, Nagano, Japan

[5] Jichi Med Univ, Dept Med, Div Hematol, Shimotsuke, Tochigi, Japan

[6] St Lukes Int Hosp, Hematooncol Dept, Tokyo, Japan

[7] Kyoto Daini Hosp, Dept Hematol, Japanese Red Cross, Kyoto, Japan

[8] Jichi Med Univ, Div Hematol, Saitama Med Ctr, Saitama, Japan

[9] Yokohama Minami Kyousai Hosp, Dept Hematol, Yokohama, Kanagawa, Japan

[10] Chiba Aoba Municipal Hosp, Dept Hematol, Chiba, Japan

[11] Chiba Univ Hosp, Dept Hematol, Chiba, Japan

[12] Eiju Gen Hop, Dept Hematol, Tokyo, Japan

[13] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan

[14] Japanese Red Cross Kyoto Daiichi Hosp, Dept Hematol, Kyoto, Japan

[15] Kyoto Prefectural Univ Med, Div Hematol & Oncol, Kyoto, Japan

[16] Toranomon Gen Hosp, Dept Hematol, Federat Natl Publ Serv Personnel Mutual Aid Assoc, Tokyo, Japan

[17] Saga Univ, Fac Med, Dept Internal Med, Div Hematol Resp Med & Oncol, Saga, Japan

[18] Natl Canc Ctr, Dept Hematopoiet Stem Cell Transplantat, Tokyo, Japan

来源：

INTERNATIONAL JOURNAL OF HEMATOLOGY | 2019年 / 110卷 / 05期

基金：

日本学术振兴会;

关键词：

FLT3-tyrosine kinase domain (FLT3-TKD); Prognosis; Frequency; Acute myeloid leukemia; INTERNAL TANDEM DUPLICATIONS; FLT3; MUTATIONS; YOUNGER ADULTS; D835; GENE-MUTATIONS; AML; IDENTIFICATION; NPM1; ABNORMALITIES; ASSOCIATION;

D O I：

10.1007/s12185-019-02720-z

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The prognostic significance of FLT3-tyrosine kinase domain (TKD) mutations remains unknown. To investigate the prognostic impact of FLT3-TKD, 676 de novo acute myeloid leukemia (AML), we retrospectively analyzed cases and conducted a review of the literature. Of the 676 de novo AML cases, 34 (5.0%) were FLT3-TKD-positive; both FLT3-TKD and FLT3-ITD were noted in only two cases (0.3%). Although no significant differences in relapse-free survival (RFS) were noted, FLT3-TKD-positive cases showed better prognoses than FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.152). For overall survival (OS), although FLT3-TKD-positive cases showed prognoses similar to those for FLT3-WT cases, their prognoses were significantly better than those of FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.032). Moreover, the 5-year OS for FLT3-TKD-positive cases was 46.1%, indicating that this as an intermediate prognosis group. Although no reports from Asia have indicated a frequency of FLT3-TKD-positive cases > 10%, several reports from Europe and the United States have indicated frequencies > 10%. This suggests the possibility that FLT3-TKD-positive cases are less common in Asia than in Europe and the United States. We anticipate that in the future, the appearance of targeting agents, such as FLT3 inhibitors, will improve the prognosis of FLT3-TKD-positive AML relative to that of FLT3-WT AML.

引用

页码：566 / 574

页数：9

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