Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

N. Moti; T. Malcolm; R. Hamoudi; S. Mian; G. Garland; C. E. Hook; G. A.A. Burke; M. A. Wasik; O. Merkel; L. Kenner; E. Laurenti; J. E. Dick; S. D. Turner

doi:10.1038/onc.2014.112

Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

N. Moti, T. Malcolm, R. Hamoudi, S. Mian, G. Garland, C. E. Hook, G. A.A. Burke, M. A. Wasik, O. Merkel, L. Kenner, E. Laurenti, J. E. Dick, S. D. Turner^*

^*Corresponding author for this work

Cancer and Genomic Sciences

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

Abstract

Cancer stem cells or tumour-propagating cells (TPCs) have been identified for a number of cancers, but data pertaining to their existence in lymphoma so far remain elusive. We show for the first time that a small subset of cells purified from human anaplastic lymphoma kinase (ALK)-positive and-negative, anaplastic large cell lymphoma cell lines and primary patient tumours using the side population (SP) technique have serial tumour-propagating capacity both in vitro and in vivo; they give rise to both themselves and the bulk tumour population as well as supporting growth of the latter through the production of soluble factors. In vivo serial dilution assays utilising a variety of model systems inclusive of human cell lines, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC frequency to vary from as many as 1/54 to 1/1336 tumour cells. In addition, the SP cells express higher levels of pluripotency-associated transcription factors and are enriched for a gene expression profile consistent with early thymic progenitors. Finally, our data show that the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.

Original language	English
Pages (from-to)	1843-1852
Number of pages	10
Journal	Oncogene
Volume	34
Issue number	14
DOIs	https://doi.org/10.1038/onc.2014.112
Publication status	Published - 12 May 2014

Bibliographical note

Funding Information:
We thank past and present members of the 'Turner lab' for their helpful discussions and critical appraisal of the manuscript. We are grateful to N Miller of the Department of Pathology, University of Cambridge, FACS facility for his assistance with SP analysis and to S Johnson of the Biological Services Unit. We are also indebted to R Jarrett, L Shield and S Crae at the Leukaemia and Lymphoma Research Virus Centre, University of Glasgow, UK, for the provision of primary disaggregated, viable patient material. We also acknowledge the support of the Sam Foye Fund and dedicate this research to the memory of Sam. SDT is a Leukaemia and Lymphoma Research Bennett Fellow (grant numbers 07006, 11051, 12065). NM receives support from the Cambridge Commonwealth Trust, University of Karachi, Pakistan, and the Elimination of Leukaemia Fund. TM is supported by a Leukaemia and Lymphoma Research Gordon Piller Studentship (Grant Number 08064).

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2014.112

Cite this

Moti, N., Malcolm, T., Hamoudi, R., Mian, S., Garland, G., Hook, C. E., Burke, G. A. A., Wasik, M. A., Merkel, O., Kenner, L., Laurenti, E., Dick, J. E., & Turner, S. D. (2014). Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin. Oncogene, 34(14), 1843-1852. https://doi.org/10.1038/onc.2014.112

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title = "Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin",

abstract = "Cancer stem cells or tumour-propagating cells (TPCs) have been identified for a number of cancers, but data pertaining to their existence in lymphoma so far remain elusive. We show for the first time that a small subset of cells purified from human anaplastic lymphoma kinase (ALK)-positive and-negative, anaplastic large cell lymphoma cell lines and primary patient tumours using the side population (SP) technique have serial tumour-propagating capacity both in vitro and in vivo; they give rise to both themselves and the bulk tumour population as well as supporting growth of the latter through the production of soluble factors. In vivo serial dilution assays utilising a variety of model systems inclusive of human cell lines, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC frequency to vary from as many as 1/54 to 1/1336 tumour cells. In addition, the SP cells express higher levels of pluripotency-associated transcription factors and are enriched for a gene expression profile consistent with early thymic progenitors. Finally, our data show that the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.",

author = "N. Moti and T. Malcolm and R. Hamoudi and S. Mian and G. Garland and Hook, {C. E.} and Burke, {G. A.A.} and Wasik, {M. A.} and O. Merkel and L. Kenner and E. Laurenti and Dick, {J. E.} and Turner, {S. D.}",

note = "Funding Information: We thank past and present members of the 'Turner lab' for their helpful discussions and critical appraisal of the manuscript. We are grateful to N Miller of the Department of Pathology, University of Cambridge, FACS facility for his assistance with SP analysis and to S Johnson of the Biological Services Unit. We are also indebted to R Jarrett, L Shield and S Crae at the Leukaemia and Lymphoma Research Virus Centre, University of Glasgow, UK, for the provision of primary disaggregated, viable patient material. We also acknowledge the support of the Sam Foye Fund and dedicate this research to the memory of Sam. SDT is a Leukaemia and Lymphoma Research Bennett Fellow (grant numbers 07006, 11051, 12065). NM receives support from the Cambridge Commonwealth Trust, University of Karachi, Pakistan, and the Elimination of Leukaemia Fund. TM is supported by a Leukaemia and Lymphoma Research Gordon Piller Studentship (Grant Number 08064). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

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Moti, N, Malcolm, T, Hamoudi, R, Mian, S, Garland, G, Hook, CE, Burke, GAA, Wasik, MA, Merkel, O, Kenner, L, Laurenti, E, Dick, JE & Turner, SD 2014, 'Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin', Oncogene, vol. 34, no. 14, pp. 1843-1852. https://doi.org/10.1038/onc.2014.112

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T1 - Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

AU - Moti, N.

AU - Malcolm, T.

AU - Hamoudi, R.

AU - Mian, S.

AU - Garland, G.

AU - Hook, C. E.

AU - Burke, G. A.A.

AU - Wasik, M. A.

AU - Merkel, O.

AU - Kenner, L.

AU - Laurenti, E.

AU - Dick, J. E.

AU - Turner, S. D.

N1 - Funding Information: We thank past and present members of the 'Turner lab' for their helpful discussions and critical appraisal of the manuscript. We are grateful to N Miller of the Department of Pathology, University of Cambridge, FACS facility for his assistance with SP analysis and to S Johnson of the Biological Services Unit. We are also indebted to R Jarrett, L Shield and S Crae at the Leukaemia and Lymphoma Research Virus Centre, University of Glasgow, UK, for the provision of primary disaggregated, viable patient material. We also acknowledge the support of the Sam Foye Fund and dedicate this research to the memory of Sam. SDT is a Leukaemia and Lymphoma Research Bennett Fellow (grant numbers 07006, 11051, 12065). NM receives support from the Cambridge Commonwealth Trust, University of Karachi, Pakistan, and the Elimination of Leukaemia Fund. TM is supported by a Leukaemia and Lymphoma Research Gordon Piller Studentship (Grant Number 08064). Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2014/5/12

Y1 - 2014/5/12

N2 - Cancer stem cells or tumour-propagating cells (TPCs) have been identified for a number of cancers, but data pertaining to their existence in lymphoma so far remain elusive. We show for the first time that a small subset of cells purified from human anaplastic lymphoma kinase (ALK)-positive and-negative, anaplastic large cell lymphoma cell lines and primary patient tumours using the side population (SP) technique have serial tumour-propagating capacity both in vitro and in vivo; they give rise to both themselves and the bulk tumour population as well as supporting growth of the latter through the production of soluble factors. In vivo serial dilution assays utilising a variety of model systems inclusive of human cell lines, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC frequency to vary from as many as 1/54 to 1/1336 tumour cells. In addition, the SP cells express higher levels of pluripotency-associated transcription factors and are enriched for a gene expression profile consistent with early thymic progenitors. Finally, our data show that the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.

AB - Cancer stem cells or tumour-propagating cells (TPCs) have been identified for a number of cancers, but data pertaining to their existence in lymphoma so far remain elusive. We show for the first time that a small subset of cells purified from human anaplastic lymphoma kinase (ALK)-positive and-negative, anaplastic large cell lymphoma cell lines and primary patient tumours using the side population (SP) technique have serial tumour-propagating capacity both in vitro and in vivo; they give rise to both themselves and the bulk tumour population as well as supporting growth of the latter through the production of soluble factors. In vivo serial dilution assays utilising a variety of model systems inclusive of human cell lines, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC frequency to vary from as many as 1/54 to 1/1336 tumour cells. In addition, the SP cells express higher levels of pluripotency-associated transcription factors and are enriched for a gene expression profile consistent with early thymic progenitors. Finally, our data show that the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.

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ER -

Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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