An investigation into the role of interleukin-15 on the growth and survival of pre-B acute lymphoblastic leukaemia cell lines

Mark Williams, Gerard Graham, Brenda Gibson, Christina Halsey

Research output: Contribution to journalMeeting abstract

Abstract

The treatment of refractory/resistant and extramedullary disease in
childhood acute lymphoblastic leukemia (ALL) remains problema-
tical. A better biological understanding of the factors involved in
leukaemic cell growth, migration and survival should aid develop-
ment of novel therapeutic approaches. Two independent genome-
wide association studies have identified polymorphisms in the
interleukin-15 (IL-15) gene as predictors of 1) leukemia development
and 2) resistance to initial therapy. In addition, IL-15 mRNA levels
have been shown to predict the likelihood of central nervous system
(CNS) relapse in childhood ALL. IL-15 is a cytokine with autocrine
and paracrine effects on T and B cell survival. It is also important for
leukocyte migration and alters adhesion molecule expression. These
characteristics support a putative role for IL-15 in leukaemic growth,
survival and/or cell migration to sites such as the CNS but this is yet
to be tested. In this study we aimed to investigate the biological
impact of IL-15 on pre-B ALL cells.
We compared the gene and protein expression of IL-15 and its
hetero-trimeric receptor (IL-15Ra, b and g) in pre-B ALL cell lines
using Taqman low density qPCR arrays and flow cytometry. We
found variable levels of expression, with high levels of both IL-15 and
its receptor seen in cell lines known to be capable of extramedullary
infiltration. Transmigration assays failed to show any chemotaxis
towards IL-15 in IL-15 receptor expressing cell lines. Using MTT, cell
growth curves and Annexin V assays we showed that addition of
exogenous IL-15 enhanced the growth of cells in vitro whilst
neutralization of the IL-15R significantly reduced their growth.
Future studies will investigate the effects of IL-15 on response to
chemotherapeutic agents.
In summary, these results support a potential role for IL-15 in
extramedullary disease and strengthen our hypothesis that IL-15 is
involved in the growth/survival of ALL cell lines.
LanguageEnglish
Article number140
Pages61
Number of pages1
JournalBritish Journal of Haematology
Volume153
Issue numberS1
DOIs
Publication statusPublished - 4 Apr 2011
Event51st Annual British Society for Haematology Meeting - Brighton, United Kingdom
Duration: 4 Apr 20116 Apr 2011

Fingerprint

Interleukin-15
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cell Line
Growth
Cell Movement
Cell Survival
Central Nervous System
Annexin A5
Genome-Wide Association Study
Biological Factors
Flow Cytometry
Leukemia
B-Lymphocytes
Cytokines
T-Lymphocytes
Gene Expression
Recurrence
Messenger RNA
Therapeutics
Genes

Keywords

  • interleukin-15
  • lymphoblastic leukaemia cells
  • lymphoblastic leukaemia

Cite this

Williams, Mark ; Graham, Gerard ; Gibson, Brenda ; Halsey, Christina. / An investigation into the role of interleukin-15 on the growth and survival of pre-B acute lymphoblastic leukaemia cell lines. In: British Journal of Haematology. 2011 ; Vol. 153, No. S1. pp. 61.
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An investigation into the role of interleukin-15 on the growth and survival of pre-B acute lymphoblastic leukaemia cell lines. / Williams, Mark; Graham, Gerard; Gibson, Brenda; Halsey, Christina.

In: British Journal of Haematology, Vol. 153, No. S1, 140, 04.04.2011, p. 61.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - An investigation into the role of interleukin-15 on the growth and survival of pre-B acute lymphoblastic leukaemia cell lines

AU - Williams, Mark

AU - Graham, Gerard

AU - Gibson, Brenda

AU - Halsey, Christina

PY - 2011/4/4

Y1 - 2011/4/4

N2 - The treatment of refractory/resistant and extramedullary disease inchildhood acute lymphoblastic leukemia (ALL) remains problema-tical. A better biological understanding of the factors involved inleukaemic cell growth, migration and survival should aid develop-ment of novel therapeutic approaches. Two independent genome-wide association studies have identified polymorphisms in theinterleukin-15 (IL-15) gene as predictors of 1) leukemia developmentand 2) resistance to initial therapy. In addition, IL-15 mRNA levelshave been shown to predict the likelihood of central nervous system(CNS) relapse in childhood ALL. IL-15 is a cytokine with autocrineand paracrine effects on T and B cell survival. It is also important forleukocyte migration and alters adhesion molecule expression. Thesecharacteristics support a putative role for IL-15 in leukaemic growth,survival and/or cell migration to sites such as the CNS but this is yetto be tested. In this study we aimed to investigate the biologicalimpact of IL-15 on pre-B ALL cells.We compared the gene and protein expression of IL-15 and itshetero-trimeric receptor (IL-15Ra, b and g) in pre-B ALL cell linesusing Taqman low density qPCR arrays and flow cytometry. Wefound variable levels of expression, with high levels of both IL-15 andits receptor seen in cell lines known to be capable of extramedullaryinfiltration. Transmigration assays failed to show any chemotaxistowards IL-15 in IL-15 receptor expressing cell lines. Using MTT, cellgrowth curves and Annexin V assays we showed that addition ofexogenous IL-15 enhanced the growth of cells in vitro whilstneutralization of the IL-15R significantly reduced their growth.Future studies will investigate the effects of IL-15 on response tochemotherapeutic agents.In summary, these results support a potential role for IL-15 inextramedullary disease and strengthen our hypothesis that IL-15 isinvolved in the growth/survival of ALL cell lines.

AB - The treatment of refractory/resistant and extramedullary disease inchildhood acute lymphoblastic leukemia (ALL) remains problema-tical. A better biological understanding of the factors involved inleukaemic cell growth, migration and survival should aid develop-ment of novel therapeutic approaches. Two independent genome-wide association studies have identified polymorphisms in theinterleukin-15 (IL-15) gene as predictors of 1) leukemia developmentand 2) resistance to initial therapy. In addition, IL-15 mRNA levelshave been shown to predict the likelihood of central nervous system(CNS) relapse in childhood ALL. IL-15 is a cytokine with autocrineand paracrine effects on T and B cell survival. It is also important forleukocyte migration and alters adhesion molecule expression. Thesecharacteristics support a putative role for IL-15 in leukaemic growth,survival and/or cell migration to sites such as the CNS but this is yetto be tested. In this study we aimed to investigate the biologicalimpact of IL-15 on pre-B ALL cells.We compared the gene and protein expression of IL-15 and itshetero-trimeric receptor (IL-15Ra, b and g) in pre-B ALL cell linesusing Taqman low density qPCR arrays and flow cytometry. Wefound variable levels of expression, with high levels of both IL-15 andits receptor seen in cell lines known to be capable of extramedullaryinfiltration. Transmigration assays failed to show any chemotaxistowards IL-15 in IL-15 receptor expressing cell lines. Using MTT, cellgrowth curves and Annexin V assays we showed that addition ofexogenous IL-15 enhanced the growth of cells in vitro whilstneutralization of the IL-15R significantly reduced their growth.Future studies will investigate the effects of IL-15 on response tochemotherapeutic agents.In summary, these results support a potential role for IL-15 inextramedullary disease and strengthen our hypothesis that IL-15 isinvolved in the growth/survival of ALL cell lines.

KW - interleukin-15

KW - lymphoblastic leukaemia cells

KW - lymphoblastic leukaemia

U2 - 10.1111/j.1365-2141.2011.08609.x

DO - 10.1111/j.1365-2141.2011.08609.x

M3 - Meeting abstract

VL - 153

SP - 61

JO - British Journal of Haematology

T2 - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - S1

M1 - 140

ER -