Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia

H.G. Otten; W.G.J. van Ginkel; A. Hagenbeek; E.J. Petersen

doi:10.1038/sj.leu.2403414

Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia

H.G. Otten, W.G.J. van Ginkel, A. Hagenbeek, E.J. Petersen

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

Abstract

Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether hematological malignancies are resistant to perforin and anti-FAS antibodies. Leukemic cells were studied from 29 patients suffering either from acute or chronic myeloid leukemia (AML or CML), acute or chronic lymphoid leukemia, or non-Hodgkin's lymphoma. An average of 49 vs 5% of specific cell killing was found when using perforin vs anti-FAS antibodies, respectively. Interestingly, resistance towards both perforin and anti-FAS antibodies was found exclusively in leukemic cells from patients with myeloid leukemia. Analysis of leukemic cells from patients with CML, suffering from leukemia relapse after HSCT and given donor lymphocyte infusion (DLI) to induce remission, indicated that the effectiveness of treatment with DLI was not associated with sensitivity of leukemic cells to perforin. In conclusion, resistance towards anti-FAS antibodies is a common phenomenon in leukemia/lymphoma, whereas perforin resistance occurs only in myeloid leukemia. However, as a single parameter, perforin resistance does not appear to be suitable to predict the outcome of DLI.

Original language	English
Pages (from-to)	1401-1405
Number of pages	5
Journal	Leukemia
Volume	18
Issue number	8
DOIs	https://doi.org/10.1038/sj.leu.2403414
Publication status	Published - Aug 2004

Keywords

Adult
Antibodies
Biomarkers
Cell Death
Cytotoxicity, Immunologic
Female
Hematologic Neoplasms
Humans
Jurkat Cells
K562 Cells
Killer Cells, Natural
Leukemia
Lymphocyte Transfusion
Male
Membrane Glycoproteins
Middle Aged
Perforin
Pore Forming Cytotoxic Proteins
Predictive Value of Tests
Prevalence
Recurrence
Tumor Cells, Cultured
fas Receptor
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1038/sj.leu.2403414

Cite this

@article{6c79552d936441e5808300a59a31ab4a,

title = "Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia",

abstract = "Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether hematological malignancies are resistant to perforin and anti-FAS antibodies. Leukemic cells were studied from 29 patients suffering either from acute or chronic myeloid leukemia (AML or CML), acute or chronic lymphoid leukemia, or non-Hodgkin's lymphoma. An average of 49 vs 5% of specific cell killing was found when using perforin vs anti-FAS antibodies, respectively. Interestingly, resistance towards both perforin and anti-FAS antibodies was found exclusively in leukemic cells from patients with myeloid leukemia. Analysis of leukemic cells from patients with CML, suffering from leukemia relapse after HSCT and given donor lymphocyte infusion (DLI) to induce remission, indicated that the effectiveness of treatment with DLI was not associated with sensitivity of leukemic cells to perforin. In conclusion, resistance towards anti-FAS antibodies is a common phenomenon in leukemia/lymphoma, whereas perforin resistance occurs only in myeloid leukemia. However, as a single parameter, perforin resistance does not appear to be suitable to predict the outcome of DLI.",

keywords = "Adult, Antibodies, Biomarkers, Cell Death, Cytotoxicity, Immunologic, Female, Hematologic Neoplasms, Humans, Jurkat Cells, K562 Cells, Killer Cells, Natural, Leukemia, Lymphocyte Transfusion, Male, Membrane Glycoproteins, Middle Aged, Perforin, Pore Forming Cytotoxic Proteins, Predictive Value of Tests, Prevalence, Recurrence, Tumor Cells, Cultured, fas Receptor, Journal Article, Research Support, Non-U.S. Gov't",

author = "H.G. Otten and {van Ginkel}, W.G.J. and A. Hagenbeek and E.J. Petersen",

year = "2004",

month = aug,

doi = "10.1038/sj.leu.2403414",

language = "English",

volume = "18",

pages = "1401--1405",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia

AU - Otten, H.G.

AU - van Ginkel, W.G.J.

AU - Hagenbeek, A.

AU - Petersen, E.J.

PY - 2004/8

Y1 - 2004/8

N2 - Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether hematological malignancies are resistant to perforin and anti-FAS antibodies. Leukemic cells were studied from 29 patients suffering either from acute or chronic myeloid leukemia (AML or CML), acute or chronic lymphoid leukemia, or non-Hodgkin's lymphoma. An average of 49 vs 5% of specific cell killing was found when using perforin vs anti-FAS antibodies, respectively. Interestingly, resistance towards both perforin and anti-FAS antibodies was found exclusively in leukemic cells from patients with myeloid leukemia. Analysis of leukemic cells from patients with CML, suffering from leukemia relapse after HSCT and given donor lymphocyte infusion (DLI) to induce remission, indicated that the effectiveness of treatment with DLI was not associated with sensitivity of leukemic cells to perforin. In conclusion, resistance towards anti-FAS antibodies is a common phenomenon in leukemia/lymphoma, whereas perforin resistance occurs only in myeloid leukemia. However, as a single parameter, perforin resistance does not appear to be suitable to predict the outcome of DLI.

AB - Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether hematological malignancies are resistant to perforin and anti-FAS antibodies. Leukemic cells were studied from 29 patients suffering either from acute or chronic myeloid leukemia (AML or CML), acute or chronic lymphoid leukemia, or non-Hodgkin's lymphoma. An average of 49 vs 5% of specific cell killing was found when using perforin vs anti-FAS antibodies, respectively. Interestingly, resistance towards both perforin and anti-FAS antibodies was found exclusively in leukemic cells from patients with myeloid leukemia. Analysis of leukemic cells from patients with CML, suffering from leukemia relapse after HSCT and given donor lymphocyte infusion (DLI) to induce remission, indicated that the effectiveness of treatment with DLI was not associated with sensitivity of leukemic cells to perforin. In conclusion, resistance towards anti-FAS antibodies is a common phenomenon in leukemia/lymphoma, whereas perforin resistance occurs only in myeloid leukemia. However, as a single parameter, perforin resistance does not appear to be suitable to predict the outcome of DLI.

KW - Adult

KW - Antibodies

KW - Biomarkers

KW - Cell Death

KW - Cytotoxicity, Immunologic

KW - Female

KW - Hematologic Neoplasms

KW - Humans

KW - Jurkat Cells

KW - K562 Cells

KW - Killer Cells, Natural

KW - Leukemia

KW - Lymphocyte Transfusion

KW - Male

KW - Membrane Glycoproteins

KW - Middle Aged

KW - Perforin

KW - Pore Forming Cytotoxic Proteins

KW - Predictive Value of Tests

KW - Prevalence

KW - Recurrence

KW - Tumor Cells, Cultured

KW - fas Receptor

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/sj.leu.2403414

DO - 10.1038/sj.leu.2403414

M3 - Article

C2 - 15215873

SN - 0887-6924

VL - 18

SP - 1401

EP - 1405

JO - Leukemia

JF - Leukemia

IS - 8

ER -

Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia

Abstract

Keywords

Access to Document

Fingerprint

Cite this