BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia

Lindsay D. Smith; Annabel R. Minton; Matthew D. Blunt; Laura I. Karydis; David A. Dutton; Karly Rai Rogers-Broadway; Rachel Dobson; Rena Liu; Faith Norster; Elizabeth Hogg; Margaret Ashton-Key; Jonathan C. Strefford; Li Jia; Dimitar G. Efremov; G. Vignir Helgason; Peter W. M. Johnson; Freda K. Stevenson; Francesco Forconi; Mark S. Cragg; David A. Tumbarello; Graham Packham; Andrew J. Steele

doi:10.1038/s41375-019-0557-y

BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia

Lindsay D. Smith (Lead / Corresponding author)
, Annabel R. Minton
, Matthew D. Blunt
, Laura I. Karydis
, David A. Dutton
, Karly Rai Rogers-Broadway
, Rachel Dobson
, Rena Liu
, Faith Norster
, Elizabeth Hogg
, Margaret Ashton-Key
, Jonathan C. Strefford
, Li Jia
, Dimitar G. Efremov
, G. Vignir Helgason
, Peter W. M. Johnson
, Freda K. Stevenson
, Francesco Forconi
, Mark S. Cragg
, David A. Tumbarello

Graham Packham, Andrew J. Steele (Lead / Corresponding author)

MRC PPU

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

18 Citations (Scopus)

137 Downloads (Pure)

Original language	English
Pages (from-to)	640-644
Number of pages	5
Journal	Leukemia
Volume	34
Issue number	2
Early online date	28 Aug 2019
DOIs	https://doi.org/10.1038/s41375-019-0557-y
Publication status	Published - Feb 2020

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

B cells
Cell signalling
Chronic lymphocytic leukaemia

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/s41375-019-0557-yLicence: CC BY

Final Published VersionFinal published version, 648 KBLicence: CC BY

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Smith, L. D., Minton, A. R., Blunt, M. D., Karydis, L. I., Dutton, D. A., Rogers-Broadway, K. R., Dobson, R., Liu, R., Norster, F., Hogg, E., Ashton-Key, M., Strefford, J. C., Jia, L., Efremov, D. G., Helgason, G. V., Johnson, P. W. M., Stevenson, F. K., Forconi, F., Cragg, M. S., ... Steele, A. J. (2020). BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia. Leukemia, 34(2), 640-644. https://doi.org/10.1038/s41375-019-0557-y

@article{2383d65db4274eafa66523e933d495a5,

title = "BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia",

keywords = "B cells, Cell signalling, Chronic lymphocytic leukaemia",

author = "Smith, \{Lindsay D.\} and Minton, \{Annabel R.\} and Blunt, \{Matthew D.\} and Karydis, \{Laura I.\} and Dutton, \{David A.\} and Rogers-Broadway, \{Karly Rai\} and Rachel Dobson and Rena Liu and Faith Norster and Elizabeth Hogg and Margaret Ashton-Key and Strefford, \{Jonathan C.\} and Li Jia and Efremov, \{Dimitar G.\} and Helgason, \{G. Vignir\} and Johnson, \{Peter W. M.\} and Stevenson, \{Freda K.\} and Francesco Forconi and Cragg, \{Mark S.\} and Tumbarello, \{David A.\} and Graham Packham and Steele, \{Andrew J.\}",

note = "Funding Information: Fig. 2 BCR-mediated autophagy is dependent on BCR signaling and provides a survival advantage to CLL cells. a CLL samples (n = 11) were treated with bead-bound isotype control antibody (IC) or anti-IgM with or without HCQ at indicated concentrations for 24 h and LC3B-II levels evaluated by immunoblotting. A representative immunoblot is shown. Blots were quantified and the mean fold change (±SEM) in LC3B-II level with each treatment vs. IC without HCQ is shown in the accompanying graph. A t-test was used for statistical analysis. b CLL samples (n = 6) were treated with or without IL-4 (10 ng/ml), in the presence or absence of HCQ, for 24 h before treatment with bead-bound IC or anti-IgM for 24 h. LC3B-II levels were evaluated by immunoblotting and the mean fold change (±SEM) in LC3B-II levels with each treatment vs. IC without HCQ is shown. A Wilcoxon{\textquoteright}s matched-pairs signed-rank test was used for statistical analysis. c CLL samples (n = 10) were treated with HCQ and a SYK (tamatinib; Tam) or BTK (ibrutinib; Ibr) inhibitor (both 5 μM) for 1 h before stimulation with bead-bound IC or anti-IgM for 24 h and the LC3B-II level evaluated by immunoblotting. Hsc70 was used as a Acknowledgements We thank Bloodwise (12044, 14040, 16003), CRUK (C2750/A23669), the patients for supplying tissue, the support from CRUK center grant (C34999/A18087), and ECMC grant (C24563/A15581). We thank Dr Ian Tracy and Dr Kathy Potter, Mrs Isla Henderson, and Ms Carina Mundy for sample characterization and storage. We thank Dr Sonya James and the University of Southampton Biomedical Imaging Unit. We thank Professor Sharon Tooze for reading the manuscript and providing scientific guidance. Finally, we acknowledge Professor Tessa Holyoake who was a collaborator on this study but who passed away before project completion.",

year = "2020",

month = feb,

doi = "10.1038/s41375-019-0557-y",

language = "English",

volume = "34",

pages = "640--644",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "2",

}

Smith, LD, Minton, AR, Blunt, MD, Karydis, LI, Dutton, DA, Rogers-Broadway, KR, Dobson, R, Liu, R, Norster, F, Hogg, E, Ashton-Key, M, Strefford, JC, Jia, L, Efremov, DG, Helgason, GV, Johnson, PWM, Stevenson, FK, Forconi, F, Cragg, MS, Tumbarello, DA, Packham, G & Steele, AJ 2020, 'BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia', Leukemia, vol. 34, no. 2, pp. 640-644. https://doi.org/10.1038/s41375-019-0557-y

TY - JOUR

T1 - BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia

AU - Smith, Lindsay D.

AU - Minton, Annabel R.

AU - Blunt, Matthew D.

AU - Karydis, Laura I.

AU - Dutton, David A.

AU - Rogers-Broadway, Karly Rai

AU - Dobson, Rachel

AU - Liu, Rena

AU - Norster, Faith

AU - Hogg, Elizabeth

AU - Ashton-Key, Margaret

AU - Strefford, Jonathan C.

AU - Jia, Li

AU - Efremov, Dimitar G.

AU - Helgason, G. Vignir

AU - Johnson, Peter W. M.

AU - Stevenson, Freda K.

AU - Forconi, Francesco

AU - Cragg, Mark S.

AU - Tumbarello, David A.

AU - Packham, Graham

AU - Steele, Andrew J.

N1 - Funding Information: Fig. 2 BCR-mediated autophagy is dependent on BCR signaling and provides a survival advantage to CLL cells. a CLL samples (n = 11) were treated with bead-bound isotype control antibody (IC) or anti-IgM with or without HCQ at indicated concentrations for 24 h and LC3B-II levels evaluated by immunoblotting. A representative immunoblot is shown. Blots were quantified and the mean fold change (±SEM) in LC3B-II level with each treatment vs. IC without HCQ is shown in the accompanying graph. A t-test was used for statistical analysis. b CLL samples (n = 6) were treated with or without IL-4 (10 ng/ml), in the presence or absence of HCQ, for 24 h before treatment with bead-bound IC or anti-IgM for 24 h. LC3B-II levels were evaluated by immunoblotting and the mean fold change (±SEM) in LC3B-II levels with each treatment vs. IC without HCQ is shown. A Wilcoxon’s matched-pairs signed-rank test was used for statistical analysis. c CLL samples (n = 10) were treated with HCQ and a SYK (tamatinib; Tam) or BTK (ibrutinib; Ibr) inhibitor (both 5 μM) for 1 h before stimulation with bead-bound IC or anti-IgM for 24 h and the LC3B-II level evaluated by immunoblotting. Hsc70 was used as a Acknowledgements We thank Bloodwise (12044, 14040, 16003), CRUK (C2750/A23669), the patients for supplying tissue, the support from CRUK center grant (C34999/A18087), and ECMC grant (C24563/A15581). We thank Dr Ian Tracy and Dr Kathy Potter, Mrs Isla Henderson, and Ms Carina Mundy for sample characterization and storage. We thank Dr Sonya James and the University of Southampton Biomedical Imaging Unit. We thank Professor Sharon Tooze for reading the manuscript and providing scientific guidance. Finally, we acknowledge Professor Tessa Holyoake who was a collaborator on this study but who passed away before project completion.

PY - 2020/2

Y1 - 2020/2

KW - B cells

KW - Cell signalling

KW - Chronic lymphocytic leukaemia

UR - https://www.scopus.com/pages/publications/85071947738

U2 - 10.1038/s41375-019-0557-y

DO - 10.1038/s41375-019-0557-y

M3 - Letter

C2 - 31462734

AN - SCOPUS:85071947738

SN - 0887-6924

VL - 34

SP - 640

EP - 644

JO - Leukemia

JF - Leukemia

IS - 2

ER -

BCR signaling contributes to autophagy regulation in chronic lymphocytic leukemia

UN SDGs

Keywords

ASJC Scopus subject areas

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