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Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia

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

Standard Standard

Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. / Alanazi, Bader; Munje, Chinmay R.; Rastogi, Namrata et al.
In: Leukemia, Vol. 34, No. 2, 2020, p. 427-440.

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

HarvardHarvard

Alanazi, B, Munje, CR, Rastogi, N, Williamson, AJK, Taylor, S, Hole, PS, Hodges, M, Doyle, M, Baker, S, Gilkes, AF, Knapper, S, Pierce, A, Whetton, AD, Darley, RL & Tonks, A 2020, 'Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia', Leukemia, vol. 34, no. 2, pp. 427-440. https://doi.org/10.1038/s41375-019-0596-4

APA

Alanazi, B., Munje, C. R., Rastogi, N., Williamson, A. J. K., Taylor, S., Hole, P. S., Hodges, M., Doyle, M., Baker, S., Gilkes, A. F., Knapper, S., Pierce, A., Whetton, A. D., Darley, R. L., & Tonks, A. (2020). Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. Leukemia, 34(2), 427-440. https://doi.org/10.1038/s41375-019-0596-4

CBE

Alanazi B, Munje CR, Rastogi N, Williamson AJK, Taylor S, Hole PS, Hodges M, Doyle M, Baker S, Gilkes AF, et al. 2020. Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. Leukemia. 34(2):427-440. https://doi.org/10.1038/s41375-019-0596-4

MLA

Alanazi, Bader et al. "Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia". Leukemia. 2020, 34(2). 427-440. https://doi.org/10.1038/s41375-019-0596-4

VancouverVancouver

Alanazi B, Munje CR, Rastogi N, Williamson AJK, Taylor S, Hole PS et al. Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. Leukemia. 2020;34(2):427-440. doi: 10.1038/s41375-019-0596-4

Author

Alanazi, Bader ; Munje, Chinmay R. ; Rastogi, Namrata et al. / Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. In: Leukemia. 2020 ; Vol. 34, No. 2. pp. 427-440.

RIS

TY - JOUR

T1 - Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia

AU - Alanazi, Bader

AU - Munje, Chinmay R.

AU - Rastogi, Namrata

AU - Williamson, Andrew J. K.

AU - Taylor, Samuel

AU - Hole, Paul S.

AU - Hodges, Marie

AU - Doyle, Michelle

AU - Baker, Sarah

AU - Gilkes, Amanda F.

AU - Knapper, Steven

AU - Pierce, Andrew

AU - Whetton, Anthony D.

AU - Darley, Richard L.

AU - Tonks, Alex

PY - 2020

Y1 - 2020

N2 - Inappropriate localization of proteins can interfere with normal cellular function and drive tumor development. To understand how this contributes to the development of acute myeloid leukemia (AML), we compared the nuclear proteome and transcriptome of AML blasts with normal human CD34+ cells. Analysis of the proteome identified networks and processes that significantly affected transcription regulation including misexpression of 11 transcription factors with seven proteins not previously implicated in AML. Transcriptome analysis identified changes in 40 transcription factors but none of these were predictive of changes at the protein level. The highest differentially expressed protein in AML nuclei compared with normal CD34+ nuclei (not previously implicated in AML) was S100A4. In an extended cohort, we found that over-expression of nuclear S100A4 was highly prevalent in AML (83%; 20/24 AML patients). Knock down of S100A4 in AML cell lines strongly impacted their survival whilst normal hemopoietic stem progenitor cells were unaffected. These data are the first analysis of the nuclear proteome in AML and have identified changes in transcription factor expression or regulation of transcription that would not have been seen at the mRNA level. These data also suggest that S100A4 is essential for AML survival and could be a therapeutic target in AML.

AB - Inappropriate localization of proteins can interfere with normal cellular function and drive tumor development. To understand how this contributes to the development of acute myeloid leukemia (AML), we compared the nuclear proteome and transcriptome of AML blasts with normal human CD34+ cells. Analysis of the proteome identified networks and processes that significantly affected transcription regulation including misexpression of 11 transcription factors with seven proteins not previously implicated in AML. Transcriptome analysis identified changes in 40 transcription factors but none of these were predictive of changes at the protein level. The highest differentially expressed protein in AML nuclei compared with normal CD34+ nuclei (not previously implicated in AML) was S100A4. In an extended cohort, we found that over-expression of nuclear S100A4 was highly prevalent in AML (83%; 20/24 AML patients). Knock down of S100A4 in AML cell lines strongly impacted their survival whilst normal hemopoietic stem progenitor cells were unaffected. These data are the first analysis of the nuclear proteome in AML and have identified changes in transcription factor expression or regulation of transcription that would not have been seen at the mRNA level. These data also suggest that S100A4 is essential for AML survival and could be a therapeutic target in AML.

U2 - 10.1038/s41375-019-0596-4

DO - 10.1038/s41375-019-0596-4

M3 - Article

VL - 34

SP - 427

EP - 440

JO - Leukemia

JF - Leukemia

SN - 1476-5551

IS - 2

ER -