Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia (original) (raw)

• Original Manuscript
• Published: 01 September 1997

Molecular Biology

• T Naoe1,
• S Yokota2,
• M Nakao2,
• S Minami3,
• K Kuriyama4,
• A Takeshita5,
• K Saito6,
• S Hasegawa7,
• S Shimodaira8,
• J Tamura9,
• C Shimazaki2,
• K Matsue10,
• H Kobayashi11,
• N Arima12,
• R Suzuki13,
• H Morishita14,
• H Saito1,
• R Ueda15 &
• …
• R Ohno5

Leukemia volume 11, pages 1447–1452 (1997)Cite this article

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Abstract

FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high ldh level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.

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Authors and Affiliations

1. Nagoya University School of Medicine, Nagoya, Japan
   H Kiyoi, T Naoe & H Saito
2. Kyoto Prefectural University of Medicine, Kyoto, Japan
   S Yokota, M Nakao & C Shimazaki
3. Japanese Red Cross, Nagoya First Hospital, Nagoya, Japan
   S Minami
4. Nagasaki University School of Medicine, Japan
   K Kuriyama
5. Hamamatsu University School of Medicine, Hamamatsu, Japan
   A Takeshita & R Ohno
6. Dokkyou University School of Medicine, Tochigi, Japan
   K Saito
7. St Marianna University School of Medicine, Yokohama, Japan
   S Hasegawa
8. Shinshu University School of Medicine, Matsumoto, Japan
   S Shimodaira
9. Gunma University School of Medicine, Maebashi, Japan
   J Tamura
10. Kameda-General Hospital, Kamogawa, Japan
    K Matsue
11. Nagano Red Cross Hospital, Nagano, Japan
    H Kobayashi
12. Kagoshima University, Faculty of Medicine, Kagoshima, Japan
    N Arima
13. Aichi Cancer Center, Nagoya, Japan
    R Suzuki
14. Suwa Red Cross Hospital, Suwa, Japan
    H Morishita
15. Nagoya City University School of Medicine, Nagoya, Japan
    R Ueda

Authors

1. H Kiyoi
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2. T Naoe
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3. S Yokota
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4. M Nakao
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5. S Minami
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6. K Kuriyama
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7. A Takeshita
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8. K Saito
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9. S Hasegawa
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10. S Shimodaira
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11. J Tamura
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12. C Shimazaki
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13. K Matsue
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14. H Kobayashi
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15. N Arima
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16. R Suzuki
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17. H Morishita
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18. H Saito
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19. R Ueda
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20. R Ohno
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Kiyoi, H., Naoe, T., Yokota, S. et al. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia.Leukemia 11, 1447–1452 (1997). https://doi.org/10.1038/sj.leu.2400756

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• Received: 07 April 1997
• Accepted: 08 May 1997
• Issue Date: 01 September 1997
• DOI: https://doi.org/10.1038/sj.leu.2400756

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