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

• Published in: International journal of hematology 2019-11, Vol.110 (5), p.566-574
• Main Authors: Sakaguchi, Masahiro, Yamaguchi, Hiroki, Kuboyama, Marika, Najima, Yuho, Usuki, Kensuke, Ueki, Toshimitsu, Oh, Iekuni, Mori, Shinichiro, Kawata, Eri, Uoshima, Nobuhiko, Kobayashi, Yutaka, Kako, Shinichi, Tajika, Kenji, Shono, Katsuhiro, Kayamori, Kensuke, Hagihara, Masao, Kanda, Junya, Uchiyama, Hitoji, Kuroda, Junya, Uchida, Naoyuki, Kubota, Yasushi, Kimura, Shinya, Kurosawa, Saiko, Date, Kenta, Nakajima, Nana, Marumo, Atsushi, Omori, Ikuko, Fujiwara, Yusuke, Terada, Kazuki, Yui, Shunsuke, Wakita, Satoshi, Arai, Kunihito, Kitano, Tomoaki, Kakihana, Kazuhiko, Kanda, Yoshinobu, Ohashi, Kazuteru, Fukuda, Takahiro, Inokuchi, Koiti
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Asia; Europe; fms-Like Tyrosine Kinase 3 - genetics; Hematology; Kinases; Leukemia; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - mortality; Literature reviews; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Myeloid leukemia; Oncology; Original Article; Prognosis; Protein Domains - genetics; Protein-tyrosine kinase; Protein-Tyrosine Kinases - genetics; Retrospective Studies; Survival; Survival Analysis; Tandem Repeat Sequences; Tyrosine; United States
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-019-02720-z

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.