Significantly Increased CD70 Up Regulation on TEL-AML Positive B Cell Precursor Acute Lymphoblastic Leukemia Cells Following CD40 Stimulation

A. Troeger, L. Glouchkova, B. Ackermann, G. Escherich, H. Hanenberg, G. Janka, S. Roettgers, U. Göbel, D. Dilloo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: TEL-AML the most common genetic alteration in childhood precursor B acute lymphoblastic leukemia (BCP-ALL) is associated with a favorable prognosis. Patients and method: We studied the expression of nerve growth factor/tumor necrosis factor receptor (NGFR/TNFR)/ligand family members on 108 primary BCP-ALL samples by flow cytometry and compared both their baseline expression and CD40-induced modulation on TEL-AML positive and negative leukemia samples. Results: Our findings demonstrate that TEL-AML positive patients exhibit a significantly higher percentage of CD40, CD27 and p75NTR positive blasts at diagnosis. This might well contribute to the improved relapse-free survival of these patients assessed in Kaplan Meier analysis as CD27 and p75NTR directly mediate apoptotic signals. Furthermore CD40 ligation enhances antigen presenting and T cell stimulatory capacity via significant up regulation of CD70 while adequate response to physiological maturation signals as indicated by concomitant down regulation of CD27 is retained in TEL-AML positive leukemia. Conclusion: These data provide novel insights in immunological control mechanisms preserved in this leukemia subtype and suggest that not only treatment with chemicals such as HDAC inhibitors but also retained in vivo response to CD40 ligation contributes to improved immune surveillance in these patients which may add to a superior relapse-free survival observed particularly in the presence of other risk factors.

Original languageEnglish (US)
Pages (from-to)332-337
Number of pages6
JournalKlinische Padiatrie
Volume226
Issue number6-7
DOIs
StatePublished - Nov 1 2014

Fingerprint

B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Up-Regulation
Leukemia
Ligation
Recurrence
Histone Deacetylase Inhibitors
Survival
Tumor Necrosis Factor Receptors
Kaplan-Meier Estimate
Nerve Growth Factor
Antigen-Presenting Cells
Flow Cytometry
Down-Regulation
Ligands
T-Lymphocytes
Therapeutics

Keywords

  • acute leukemia
  • immune response
  • TEL-AML rearrangements
  • TNF receptors

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Significantly Increased CD70 Up Regulation on TEL-AML Positive B Cell Precursor Acute Lymphoblastic Leukemia Cells Following CD40 Stimulation. / Troeger, A.; Glouchkova, L.; Ackermann, B.; Escherich, G.; Hanenberg, H.; Janka, G.; Roettgers, S.; Göbel, U.; Dilloo, D.

In: Klinische Padiatrie, Vol. 226, No. 6-7, 01.11.2014, p. 332-337.

Research output: Contribution to journalArticle

Troeger, A, Glouchkova, L, Ackermann, B, Escherich, G, Hanenberg, H, Janka, G, Roettgers, S, Göbel, U & Dilloo, D 2014, 'Significantly Increased CD70 Up Regulation on TEL-AML Positive B Cell Precursor Acute Lymphoblastic Leukemia Cells Following CD40 Stimulation', Klinische Padiatrie, vol. 226, no. 6-7, pp. 332-337. https://doi.org/10.1055/s-0034-1374640
Troeger, A. ; Glouchkova, L. ; Ackermann, B. ; Escherich, G. ; Hanenberg, H. ; Janka, G. ; Roettgers, S. ; Göbel, U. ; Dilloo, D. / Significantly Increased CD70 Up Regulation on TEL-AML Positive B Cell Precursor Acute Lymphoblastic Leukemia Cells Following CD40 Stimulation. In: Klinische Padiatrie. 2014 ; Vol. 226, No. 6-7. pp. 332-337.
@article{058ffa1d80374ee8abcf423190b582f5,
title = "Significantly Increased CD70 Up Regulation on TEL-AML Positive B Cell Precursor Acute Lymphoblastic Leukemia Cells Following CD40 Stimulation",
abstract = "Background: TEL-AML the most common genetic alteration in childhood precursor B acute lymphoblastic leukemia (BCP-ALL) is associated with a favorable prognosis. Patients and method: We studied the expression of nerve growth factor/tumor necrosis factor receptor (NGFR/TNFR)/ligand family members on 108 primary BCP-ALL samples by flow cytometry and compared both their baseline expression and CD40-induced modulation on TEL-AML positive and negative leukemia samples. Results: Our findings demonstrate that TEL-AML positive patients exhibit a significantly higher percentage of CD40, CD27 and p75NTR positive blasts at diagnosis. This might well contribute to the improved relapse-free survival of these patients assessed in Kaplan Meier analysis as CD27 and p75NTR directly mediate apoptotic signals. Furthermore CD40 ligation enhances antigen presenting and T cell stimulatory capacity via significant up regulation of CD70 while adequate response to physiological maturation signals as indicated by concomitant down regulation of CD27 is retained in TEL-AML positive leukemia. Conclusion: These data provide novel insights in immunological control mechanisms preserved in this leukemia subtype and suggest that not only treatment with chemicals such as HDAC inhibitors but also retained in vivo response to CD40 ligation contributes to improved immune surveillance in these patients which may add to a superior relapse-free survival observed particularly in the presence of other risk factors.",
keywords = "acute leukemia, immune response, TEL-AML rearrangements, TNF receptors",
author = "A. Troeger and L. Glouchkova and B. Ackermann and G. Escherich and H. Hanenberg and G. Janka and S. Roettgers and U. G{\"o}bel and D. Dilloo",
year = "2014",
month = "11",
day = "1",
doi = "10.1055/s-0034-1374640",
language = "English (US)",
volume = "226",
pages = "332--337",
journal = "Klinische Padiatrie",
issn = "0300-8630",
publisher = "Georg Thieme Verlag",
number = "6-7",

}

TY - JOUR

T1 - Significantly Increased CD70 Up Regulation on TEL-AML Positive B Cell Precursor Acute Lymphoblastic Leukemia Cells Following CD40 Stimulation

AU - Troeger, A.

AU - Glouchkova, L.

AU - Ackermann, B.

AU - Escherich, G.

AU - Hanenberg, H.

AU - Janka, G.

AU - Roettgers, S.

AU - Göbel, U.

AU - Dilloo, D.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Background: TEL-AML the most common genetic alteration in childhood precursor B acute lymphoblastic leukemia (BCP-ALL) is associated with a favorable prognosis. Patients and method: We studied the expression of nerve growth factor/tumor necrosis factor receptor (NGFR/TNFR)/ligand family members on 108 primary BCP-ALL samples by flow cytometry and compared both their baseline expression and CD40-induced modulation on TEL-AML positive and negative leukemia samples. Results: Our findings demonstrate that TEL-AML positive patients exhibit a significantly higher percentage of CD40, CD27 and p75NTR positive blasts at diagnosis. This might well contribute to the improved relapse-free survival of these patients assessed in Kaplan Meier analysis as CD27 and p75NTR directly mediate apoptotic signals. Furthermore CD40 ligation enhances antigen presenting and T cell stimulatory capacity via significant up regulation of CD70 while adequate response to physiological maturation signals as indicated by concomitant down regulation of CD27 is retained in TEL-AML positive leukemia. Conclusion: These data provide novel insights in immunological control mechanisms preserved in this leukemia subtype and suggest that not only treatment with chemicals such as HDAC inhibitors but also retained in vivo response to CD40 ligation contributes to improved immune surveillance in these patients which may add to a superior relapse-free survival observed particularly in the presence of other risk factors.

AB - Background: TEL-AML the most common genetic alteration in childhood precursor B acute lymphoblastic leukemia (BCP-ALL) is associated with a favorable prognosis. Patients and method: We studied the expression of nerve growth factor/tumor necrosis factor receptor (NGFR/TNFR)/ligand family members on 108 primary BCP-ALL samples by flow cytometry and compared both their baseline expression and CD40-induced modulation on TEL-AML positive and negative leukemia samples. Results: Our findings demonstrate that TEL-AML positive patients exhibit a significantly higher percentage of CD40, CD27 and p75NTR positive blasts at diagnosis. This might well contribute to the improved relapse-free survival of these patients assessed in Kaplan Meier analysis as CD27 and p75NTR directly mediate apoptotic signals. Furthermore CD40 ligation enhances antigen presenting and T cell stimulatory capacity via significant up regulation of CD70 while adequate response to physiological maturation signals as indicated by concomitant down regulation of CD27 is retained in TEL-AML positive leukemia. Conclusion: These data provide novel insights in immunological control mechanisms preserved in this leukemia subtype and suggest that not only treatment with chemicals such as HDAC inhibitors but also retained in vivo response to CD40 ligation contributes to improved immune surveillance in these patients which may add to a superior relapse-free survival observed particularly in the presence of other risk factors.

KW - acute leukemia

KW - immune response

KW - TEL-AML rearrangements

KW - TNF receptors

UR - http://www.scopus.com/inward/record.url?scp=84941122480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941122480&partnerID=8YFLogxK

U2 - 10.1055/s-0034-1374640

DO - 10.1055/s-0034-1374640

M3 - Article

C2 - 25062112

AN - SCOPUS:84941122480

VL - 226

SP - 332

EP - 337

JO - Klinische Padiatrie

JF - Klinische Padiatrie

SN - 0300-8630

IS - 6-7

ER -