In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor

Jianbiao Zhou; Jiaying Khng; Viraj J. Jasinghe; Chonglei Bi; Chiew Hoon Serene Neo; Mengfei Pan; Lai Fong Poon; Zhigang Xie; Hanry Yu; Allen Eng Juh Yeoh; Yi Lu; Keith B. Glaser; Daniel H. Albert; Steven K. Davidsen; Chien Shing Chen

doi:10.1016/j.leukres.2007.11.025

In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor

Jianbiao Zhou
, Jiaying Khng
, Viraj J. Jasinghe
, Chonglei Bi
, Chiew Hoon Serene Neo
, Mengfei Pan
, Lai Fong Poon
, Zhigang Xie
, Hanry Yu
, Allen Eng Juh Yeoh
, Yi Lu
, Keith B. Glaser
, Daniel H. Albert
, Steven K. Davidsen
, Chien Shing Chen

Research output: Contribution to journal › Article › peer-review

Abstract

Neoangiogenesis plays an important role in leukemogenesis. We investigated the in vivo anti-leukemic effect of ABT-869 against AML with wild-type FLT3 using RFP transfected HL60 cells with in vivo imaging technology on both the subcutaneous and systemic leukemia xenograft models. ABT-869 showed a five-fold inhibition of tumor growth in comparison with vehicle control. IHC analysis revealed that ABT-869 decreased p-VEGFR1, Ki-67 labeling index, VEGF and remarkably increased apoptotic cells in the xenograft models. ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3.

Original language	English
Pages (from-to)	1091-1100
Number of pages	10
Journal	Leukemia Research
Volume	32
Issue number	7
DOIs	https://doi.org/10.1016/j.leukres.2007.11.025
State	Published - Jul 2008

ASJC Scopus Subject Areas

Hematology
Oncology
Cancer Research

Keywords

Acute myeloid leukemia
In vivo
Tyrosine kinase inhibitor
Whole-body imaging technology
Wild-type FLT3 receptor

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10.1016/j.leukres.2007.11.025

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Zhou, J., Khng, J., Jasinghe, V. J., Bi, C., Neo, C. H. S., Pan, M., Poon, L. F., Xie, Z., Yu, H., Yeoh, A. E. J., Lu, Y., Glaser, K. B., Albert, D. H., Davidsen, S. K., & Chen, C. S. (2008). In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor. Leukemia Research, 32(7), 1091-1100. https://doi.org/10.1016/j.leukres.2007.11.025

Zhou, J, Khng, J, Jasinghe, VJ, Bi, C, Neo, CHS, Pan, M, Poon, LF, Xie, Z, Yu, H, Yeoh, AEJ, Lu, Y, Glaser, KB, Albert, DH, Davidsen, SK & Chen, CS 2008, 'In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor', Leukemia Research, vol. 32, no. 7, pp. 1091-1100. https://doi.org/10.1016/j.leukres.2007.11.025

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title = "In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor",

abstract = "Neoangiogenesis plays an important role in leukemogenesis. We investigated the in vivo anti-leukemic effect of ABT-869 against AML with wild-type FLT3 using RFP transfected HL60 cells with in vivo imaging technology on both the subcutaneous and systemic leukemia xenograft models. ABT-869 showed a five-fold inhibition of tumor growth in comparison with vehicle control. IHC analysis revealed that ABT-869 decreased p-VEGFR1, Ki-67 labeling index, VEGF and remarkably increased apoptotic cells in the xenograft models. ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3.",

keywords = "Acute myeloid leukemia, In vivo, Tyrosine kinase inhibitor, Whole-body imaging technology, Wild-type FLT3 receptor",

author = "Jianbiao Zhou and Jiaying Khng and Jasinghe, \{Viraj J.\} and Chonglei Bi and Neo, \{Chiew Hoon Serene\} and Mengfei Pan and Poon, \{Lai Fong\} and Zhigang Xie and Hanry Yu and Yeoh, \{Allen Eng Juh\} and Yi Lu and Glaser, \{Keith B.\} and Albert, \{Daniel H.\} and Davidsen, \{Steven K.\} and Chen, \{Chien Shing\}",

note = "Funding Information: This work was supported by grants from Singapore Cancer Syndicate (AN0038 and TN0031). Three of the authors (K.B.G., D.H.A. and S.K.D.) are employees of Abbott Laboratories, whose potential product was studied in the present work. We would like to thank Dr. Robert M. Hoffman from Anticancer, Inc., San Diego, CA, for his support in training J.Z. about OV100 Imaging System at an earlier time point. ",

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AU - Bi, Chonglei

AU - Neo, Chiew Hoon Serene

AU - Pan, Mengfei

AU - Poon, Lai Fong

AU - Xie, Zhigang

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AU - Yeoh, Allen Eng Juh

AU - Lu, Yi

AU - Glaser, Keith B.

AU - Albert, Daniel H.

AU - Davidsen, Steven K.

AU - Chen, Chien Shing

N1 - Funding Information: This work was supported by grants from Singapore Cancer Syndicate (AN0038 and TN0031). Three of the authors (K.B.G., D.H.A. and S.K.D.) are employees of Abbott Laboratories, whose potential product was studied in the present work. We would like to thank Dr. Robert M. Hoffman from Anticancer, Inc., San Diego, CA, for his support in training J.Z. about OV100 Imaging System at an earlier time point.

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N2 - Neoangiogenesis plays an important role in leukemogenesis. We investigated the in vivo anti-leukemic effect of ABT-869 against AML with wild-type FLT3 using RFP transfected HL60 cells with in vivo imaging technology on both the subcutaneous and systemic leukemia xenograft models. ABT-869 showed a five-fold inhibition of tumor growth in comparison with vehicle control. IHC analysis revealed that ABT-869 decreased p-VEGFR1, Ki-67 labeling index, VEGF and remarkably increased apoptotic cells in the xenograft models. ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3.

AB - Neoangiogenesis plays an important role in leukemogenesis. We investigated the in vivo anti-leukemic effect of ABT-869 against AML with wild-type FLT3 using RFP transfected HL60 cells with in vivo imaging technology on both the subcutaneous and systemic leukemia xenograft models. ABT-869 showed a five-fold inhibition of tumor growth in comparison with vehicle control. IHC analysis revealed that ABT-869 decreased p-VEGFR1, Ki-67 labeling index, VEGF and remarkably increased apoptotic cells in the xenograft models. ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3.

KW - Acute myeloid leukemia

KW - In vivo

KW - Tyrosine kinase inhibitor

KW - Whole-body imaging technology

KW - Wild-type FLT3 receptor

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In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor

Abstract

ASJC Scopus Subject Areas

Keywords

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