Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights

Bella Patel, Aditi Dey, Ehsan Ghorani, Shaji K Kumar, Yogeshkumar Malam, Lena Rai, Andrew J. Steele, Jennifer Thomson, R. Gitendra Wickremasinghe, Yu Zhang, Anna Z. Castleton, Adele K. Fielding

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Clinical trials using vaccine measles virus (MV) as anticancer therapy are already underway. We compared the oncolytic potential of MV in two B-cell malignancies; adult acute lymphoblastic leukemia (ALL, an aggressive leukemia) and chronic lymphocytic leukemia (CLL, an indolent leukemia overexpressing Bcl-2) using patient-derived material. In vitro, distinct cytopathological effects were observed between MV-infected primary ALL and CLL cells, with large multinucleated syncytia forming in ALL cultures compared to minimal cell-to-cell fusion in infected CLL cells. Cell viability and immunoblotting studies confirmed rapid cell death in MV-infected ALL cultures and slower MV oncolysis of CLL cells. In cell lines, overexpression of Bcl-2 diminished MV-induced cell death providing a possible mechanism for the slower kinetic of MV oncolysis in CLL. In vivo, intratumoral MV treatment of established subcutaneous ALL xenografts had striking antitumor activity leading to complete resolution of all tumors. The antitumor activity of MV was also evident in disseminated ALL xenograft models. In summary, both ALL and CLL are targets for MV-mediated lysis albeit with different kinetics. The marked sensitivity of both primary ALL cells and ALL xenografts to MV oncolysis highlights the tremendous potential of MV as a novel replicating-virus therapy for adult ALL.

Original languageEnglish (US)
Pages (from-to)1034-1040
Number of pages7
JournalMolecular Therapy
Volume19
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Measles virus
Measles
B-Lymphocytes
Neoplasms
Heterografts
Leukemia
Cell Death
Cell Fusion
B-Cell Chronic Lymphocytic Leukemia
Giant Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoblotting
Cell Survival
Therapeutics
Vaccines

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights. / Patel, Bella; Dey, Aditi; Ghorani, Ehsan; Kumar, Shaji K; Malam, Yogeshkumar; Rai, Lena; Steele, Andrew J.; Thomson, Jennifer; Wickremasinghe, R. Gitendra; Zhang, Yu; Castleton, Anna Z.; Fielding, Adele K.

In: Molecular Therapy, Vol. 19, No. 6, 06.2011, p. 1034-1040.

Research output: Contribution to journalArticle

Patel, B, Dey, A, Ghorani, E, Kumar, SK, Malam, Y, Rai, L, Steele, AJ, Thomson, J, Wickremasinghe, RG, Zhang, Y, Castleton, AZ & Fielding, AK 2011, 'Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights', Molecular Therapy, vol. 19, no. 6, pp. 1034-1040. https://doi.org/10.1038/mt.2011.44
Patel, Bella ; Dey, Aditi ; Ghorani, Ehsan ; Kumar, Shaji K ; Malam, Yogeshkumar ; Rai, Lena ; Steele, Andrew J. ; Thomson, Jennifer ; Wickremasinghe, R. Gitendra ; Zhang, Yu ; Castleton, Anna Z. ; Fielding, Adele K. / Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights. In: Molecular Therapy. 2011 ; Vol. 19, No. 6. pp. 1034-1040.
@article{59a57ad7b8aa46e7b9cd5af8f4051a24,
title = "Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights",
abstract = "Clinical trials using vaccine measles virus (MV) as anticancer therapy are already underway. We compared the oncolytic potential of MV in two B-cell malignancies; adult acute lymphoblastic leukemia (ALL, an aggressive leukemia) and chronic lymphocytic leukemia (CLL, an indolent leukemia overexpressing Bcl-2) using patient-derived material. In vitro, distinct cytopathological effects were observed between MV-infected primary ALL and CLL cells, with large multinucleated syncytia forming in ALL cultures compared to minimal cell-to-cell fusion in infected CLL cells. Cell viability and immunoblotting studies confirmed rapid cell death in MV-infected ALL cultures and slower MV oncolysis of CLL cells. In cell lines, overexpression of Bcl-2 diminished MV-induced cell death providing a possible mechanism for the slower kinetic of MV oncolysis in CLL. In vivo, intratumoral MV treatment of established subcutaneous ALL xenografts had striking antitumor activity leading to complete resolution of all tumors. The antitumor activity of MV was also evident in disseminated ALL xenograft models. In summary, both ALL and CLL are targets for MV-mediated lysis albeit with different kinetics. The marked sensitivity of both primary ALL cells and ALL xenografts to MV oncolysis highlights the tremendous potential of MV as a novel replicating-virus therapy for adult ALL.",
author = "Bella Patel and Aditi Dey and Ehsan Ghorani and Kumar, {Shaji K} and Yogeshkumar Malam and Lena Rai and Steele, {Andrew J.} and Jennifer Thomson and Wickremasinghe, {R. Gitendra} and Yu Zhang and Castleton, {Anna Z.} and Fielding, {Adele K.}",
year = "2011",
month = "6",
doi = "10.1038/mt.2011.44",
language = "English (US)",
volume = "19",
pages = "1034--1040",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights

AU - Patel, Bella

AU - Dey, Aditi

AU - Ghorani, Ehsan

AU - Kumar, Shaji K

AU - Malam, Yogeshkumar

AU - Rai, Lena

AU - Steele, Andrew J.

AU - Thomson, Jennifer

AU - Wickremasinghe, R. Gitendra

AU - Zhang, Yu

AU - Castleton, Anna Z.

AU - Fielding, Adele K.

PY - 2011/6

Y1 - 2011/6

N2 - Clinical trials using vaccine measles virus (MV) as anticancer therapy are already underway. We compared the oncolytic potential of MV in two B-cell malignancies; adult acute lymphoblastic leukemia (ALL, an aggressive leukemia) and chronic lymphocytic leukemia (CLL, an indolent leukemia overexpressing Bcl-2) using patient-derived material. In vitro, distinct cytopathological effects were observed between MV-infected primary ALL and CLL cells, with large multinucleated syncytia forming in ALL cultures compared to minimal cell-to-cell fusion in infected CLL cells. Cell viability and immunoblotting studies confirmed rapid cell death in MV-infected ALL cultures and slower MV oncolysis of CLL cells. In cell lines, overexpression of Bcl-2 diminished MV-induced cell death providing a possible mechanism for the slower kinetic of MV oncolysis in CLL. In vivo, intratumoral MV treatment of established subcutaneous ALL xenografts had striking antitumor activity leading to complete resolution of all tumors. The antitumor activity of MV was also evident in disseminated ALL xenograft models. In summary, both ALL and CLL are targets for MV-mediated lysis albeit with different kinetics. The marked sensitivity of both primary ALL cells and ALL xenografts to MV oncolysis highlights the tremendous potential of MV as a novel replicating-virus therapy for adult ALL.

AB - Clinical trials using vaccine measles virus (MV) as anticancer therapy are already underway. We compared the oncolytic potential of MV in two B-cell malignancies; adult acute lymphoblastic leukemia (ALL, an aggressive leukemia) and chronic lymphocytic leukemia (CLL, an indolent leukemia overexpressing Bcl-2) using patient-derived material. In vitro, distinct cytopathological effects were observed between MV-infected primary ALL and CLL cells, with large multinucleated syncytia forming in ALL cultures compared to minimal cell-to-cell fusion in infected CLL cells. Cell viability and immunoblotting studies confirmed rapid cell death in MV-infected ALL cultures and slower MV oncolysis of CLL cells. In cell lines, overexpression of Bcl-2 diminished MV-induced cell death providing a possible mechanism for the slower kinetic of MV oncolysis in CLL. In vivo, intratumoral MV treatment of established subcutaneous ALL xenografts had striking antitumor activity leading to complete resolution of all tumors. The antitumor activity of MV was also evident in disseminated ALL xenograft models. In summary, both ALL and CLL are targets for MV-mediated lysis albeit with different kinetics. The marked sensitivity of both primary ALL cells and ALL xenografts to MV oncolysis highlights the tremendous potential of MV as a novel replicating-virus therapy for adult ALL.

UR - http://www.scopus.com/inward/record.url?scp=79957909618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957909618&partnerID=8YFLogxK

U2 - 10.1038/mt.2011.44

DO - 10.1038/mt.2011.44

M3 - Article

C2 - 21427708

AN - SCOPUS:79957909618

VL - 19

SP - 1034

EP - 1040

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 6

ER -