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

Masahiro Sakaguchi¹, Hiroki Yamaguchi², Marika Kuboyama¹, Yuho Najima³, Kensuke Usuki⁴, Toshimitsu Ueki⁵, Iekuni Oh⁶, Shinichiro Mori⁷, Eri Kawata^{8

9}, Nobuhiko Uoshima⁸, Yutaka Kobayashi⁸, Shinichi Kako¹⁰, Kenji Tajika¹¹, Katsuhiro Shono¹², Kensuke Kayamori¹³, Masao Hagihara¹⁴, Junya Kanda¹⁵, Hitoji Uchiyama¹⁶, Junya Kuroda⁹, Naoyuki Uchida¹⁷, Yasushi Kubota¹⁸, Shinya Kimura¹⁸, Saiko Kurosawa¹⁹, Kenta Date¹, Nana Nakajima¹, Atsushi Marumo¹, Ikuko Omori¹, Yusuke Fujiwara¹, Kazuki Terada¹, Shunsuke Yui¹, Satoshi Wakita¹, Kunihito Arai¹, Tomoaki Kitano¹, Kazuhiko Kakihana³, Yoshinobu Kanda^{6

10}, Kazuteru Ohashi³, Takahiro Fukuda¹⁹, Koiti Inokuchi¹

Affiliations

¹ Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan.
² Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan. y-hiroki@fd6.so-net.ne.jp.
³ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
⁴ Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.
⁵ Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan.
⁶ Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
⁷ Hemato-Oncology Department, St. Luke's International Hospital, Tokyo, Japan.
⁸ Department of Hematology, Japanese Red Cross, Kyoto Daini Hospital, Kyoto, Japan.
⁹ Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹⁰ Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
¹¹ Department of Hematology, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan.
¹² Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan.
¹³ Department of Hematology, Chiba University Hospital, Chiba, Japan.
¹⁴ Department of Hematology, Eiju General Hopital, Tokyo, Japan.
¹⁵ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁶ Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
¹⁷ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan.
¹⁸ Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
¹⁹ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

PMID: 31432396
DOI: 10.1007/s12185-019-02720-z

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

Masahiro Sakaguchi et al. Int J Hematol. 2019 Nov.

. 2019 Nov;110(5):566-574.

doi: 10.1007/s12185-019-02720-z. Epub 2019 Aug 20.

Authors

Affiliations

¹ Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan.
² Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan. y-hiroki@fd6.so-net.ne.jp.
³ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
⁴ Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.
⁵ Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan.
⁶ Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
⁷ Hemato-Oncology Department, St. Luke's International Hospital, Tokyo, Japan.
⁸ Department of Hematology, Japanese Red Cross, Kyoto Daini Hospital, Kyoto, Japan.
⁹ Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹⁰ Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
¹¹ Department of Hematology, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan.
¹² Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan.
¹³ Department of Hematology, Chiba University Hospital, Chiba, Japan.
¹⁴ Department of Hematology, Eiju General Hopital, Tokyo, Japan.
¹⁵ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁶ Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
¹⁷ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan.
¹⁸ Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
¹⁹ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

PMID: 31432396
DOI: 10.1007/s12185-019-02720-z

Abstract

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.

Keywords: Acute myeloid leukemia; FLT3-tyrosine kinase domain (FLT3-TKD); Frequency; Prognosis.

PubMed Disclaimer

References

1. Lancet Oncol. 2017 Aug;18(8):1061-1075 - PubMed
1. Eur J Haematol. 2004 May;72(5):307-13 - PubMed
1. Blood. 2002 Nov 1;100(9):3423-5 - PubMed
1. Cancer Genet Cytogenet. 2005 Oct 15;162(2):127-34 - PubMed
1. Clin Lymphoma Myeloma Leuk. 2018 Dec;18(12):e545-e550 - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Springer
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous