DOI: 10.1182/blood.v91.1.22. Lack of Interferon Consensus Sequence Binding Protein (ICSBP) Transcripts in Human Myeloid Leukemias

Lack of Interferon Consensus Sequence Binding Protein (ICSBP) Transcripts in Human Myeloid Leukemias

10.1182/blood.v91.1.22

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

AbstractInterferon consensus sequence binding protein (ICSBP) was first identified as a transcription factor of the interferon (IFN) regulatory factor family (IRF) which regulates expression of IFN-dependent genes by binding to DNA at specific sites, IFN-stimulated responsive elements. Analysis of ICSBP-deficient mice showed hematologic alterations similar to chronic myelogenous leukemia (CML) in humans and suggested a novel role for ICSBP in regulating proliferation and differentiation of hematopoietic progenitor cells. Here we show that ICSBP-mRNA expression is impaired in human myeloid leukemias: 27 of 34 CML patients (79%) and 21 of 32 patients with acute myeloid leukemia (AML) (66%) showed very low or absent transcript numbers of ICSBP. In contrast, only 2 of 33 normal volunteers (6%) showed low transcription of ICSBP(P < .0001 both for CML and AML values). The lack of expression was not associated with lack of lymphatic cells, which normally have been shown to express ICSBP at the highest level. More detailed analysis showed an absence of ICSBP-mRNA also in sorted B cells derived from CML patients. To analyze whetherICSBP may be induced in leukemic cells, ex vivoexperiments using a known inducer of ICSBP, IFN-γ, were performed. Ex vivo treatment of primary CML cells using IFN-γ resulted in induction of ICSBP transcripts. Furthermore, samples of CML patients during IFN-α treatment were analyzed. In 11 of 12 CML patients ICSBP-mRNA was inducible upon in vivo treatment with IFN-α, but decreased with progression of CML. Stable transfection of K-562 cell line with ICSBP led to no difference in bcr-abl expression in vitro, although two patients showed an inverse correlation between bcr-abl andICSBP in vivo. These data suggest that lack of ICSBPmay have an important role also in human myeloid leukemogenesis.

Bibliography

Schmidt, M., Nagel, S., Proba, J., Thiede, C., Ritter, M., Waring, J. F., Rosenbauer, F., Huhn, D., Wittig, B., Horak, I., & Neubauer, A. (1998). Lack of Interferon Consensus Sequence Binding Protein (ICSBP) Transcripts in Human Myeloid Leukemias. Blood, 91(1), 22â29.

Authors 11

Manuel Schmidt (first)
Stefan Nagel (additional)
Jutta Proba (additional)
Christian Thiede (additional)
Markus Ritter (additional)
Jeffrey F. Waring (additional)
Frank Rosenbauer (additional)
Dieter Huhn (additional)
Burghardt Wittig (additional)
Ivan Horak (additional)
Andreas Neubauer (additional)

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Dates

Type	When
Created	5 years, 10 months ago (Oct. 14, 2019, 8:56 a.m.)
Deposited	1 year, 11 months ago (Sept. 21, 2023, 12:58 p.m.)
Indexed	4 months, 3 weeks ago (March 31, 2025, 1:08 a.m.)
Issued	27 years, 7 months ago (Jan. 1, 1998)
Published	27 years, 7 months ago (Jan. 1, 1998)
Published Print	27 years, 7 months ago (Jan. 1, 1998)

Funders 0

None

BibTeX

@article{Schmidt_1998, title={Lack of Interferon Consensus Sequence Binding Protein (ICSBP) Transcripts in Human Myeloid Leukemias}, volume={91}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v91.1.22}, DOI={10.1182/blood.v91.1.22}, number={1}, journal={Blood}, publisher={American Society of Hematology}, author={Schmidt, Manuel and Nagel, Stefan and Proba, Jutta and Thiede, Christian and Ritter, Markus and Waring, Jeffrey F. and Rosenbauer, Frank and Huhn, Dieter and Wittig, Burghardt and Horak, Ivan and Neubauer, Andreas}, year={1998}, month=jan, pages={22–29} }

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