The PEBP2β/CBFβ-SMMHC chimeric protein is localized both in the cell membrane and nuclear subfractions of leukemic cells carrying chromosomal inversion 16

Kanto, Satoru; Chiba, Natsuko; Tanaka, Yuta; Fujita, S; Kamada, Nanao; Yoshikawa, Kazuyuki; Fukuzaki, Atsushi; Orikasa, Seiichi; Watanabe, Toshio; Satake, Masanobu

doi:10.1038/sj.leu.2401821

Cited by 18 publications

(24 citation statements)

References 33 publications

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“…The unfractionated thymocytes in which DP cells occupy 80% of the population gave rise to the 56/58-kDa band (lane 1). This band represents the AML1/Runx1 gene product as described previously (21,27). The extracts prepared from the purified CD4 SP and CD8 SP thymocytes likewise contained the 56/58-kDa component to a similar degree (lanes 2 and 3).…”

Section: Aml1 Protein Is Expressed Both In Cd8 Sp and Cd4 Sp Thymocytesmentioning

confidence: 62%

“…However, there is one notable difference between the case of AML1 and that of Runx2/ Cbfa1. In immunoblot analysis, we could detect the endogenous AML1 gene product of 56/58 kDa in the fractions of thymocytes, whereas a band of 62 kDa, which is estimated to be the size of Runx2/Cbfa1 (27), was missing in the lanes of Fig. 8.…”

Section: Discussionmentioning

confidence: 93%

“…The anti-AML1 peptide Ab used here cross-reacts with the products of mammalian runt gene family via their carboxyl-terminal ends (27). It is noteworthy in this sense that for the CD8 SP, but not CD4 SP, thymocytes an additional band of 52 kDa was detected.…”

Section: Aml1 Protein Is Expressed Both In Cd8 Sp and Cd4 Sp Thymocytesmentioning

confidence: 89%

“…The monoclonal anti-HA Ab, 3F10, was obtained from Roche Diagnostics (Indianapolis, IN). Raising and characterization of anti-AML1 peptide Ab were described previously (27). Briefly, the antiserum was raised against the carboxyl-terminal, 15 aa residues of murine AML1b/PEBP2␣B protein.…”

Section: Immunoblot Analysismentioning

confidence: 99%

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Overexpression of AML1 Transcription Factor Drives Thymocytes into the CD8 Single-Positive Lineage

Hayashi

Abe

Watanabe

et al. 2001

The Journal of Immunology

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To understand the gene regulation involved in the development of single-positive (SP) thymocytes, we generated transgenic mice in which the AML1 transcription factor is overexpressed. In these mice the number of CD8 SP thymocytes was greatly increased, and this continued to be true even when MHC class I was absent. This promotion to the CD8 SP lineage was not, however, observed when both class I and class II were absent. Furthermore, even thymocytes carrying MHC class II-restricted TCR differentiated into the CD8 SP lineage when AML1 was overexpressed. The selected CD8 SP cells were, however, unable to mature, as judged by the expression level of heat-stable Ag. Thus, overexpression of AML1 is able to skew class II-restricted thymocytes into the CD8 SP lineage, but not to drive the maturation of resulting selected CD8 SP cells.

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Section: Aml1 Protein Is Expressed Both In Cd8 Sp and Cd4 Sp Thymocytesmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 93%

Section: Aml1 Protein Is Expressed Both In Cd8 Sp and Cd4 Sp Thymocytesmentioning

confidence: 89%

Section: Immunoblot Analysismentioning

confidence: 99%

See 2 more Smart Citations

Overexpression of AML1 Transcription Factor Drives Thymocytes into the CD8 Single-Positive Lineage

Hayashi

Abe

Watanabe

et al. 2001

The Journal of Immunology

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“…6 The chimeric gene CBFb-MYH11 fuses most of the 5 0 coding region of CBFb in frame with the 3 0 portion of MYH11, resulting in the production of the chimeric protein CBFb-MYH11 in leukemic cells 7,8 and abnormal eosinophils, indicating that the latter also derive from the leukemic clone. 9 Cytogenetically, the CBFb-MYH11 fusion gene may be associated with trisomy 8, 21, and 22 and, less frequently, with deletion of chromosome 7q.…”

mentioning

confidence: 99%

Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping

et al. 2007

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Acute myeloid leukemia with inv(16)(p13q22), also known as M4Eo, is a distinct type of leukemia with characteristic clinicopathologic and cytogenetic features. Patients with M4Eo have monocytosis, high blast counts, and abnormal bone marrow eosinophils that contain large basophilic granules. The inv(16)(p13q22) or, less commonly, the t(16;16)(p13;q22) causes fusion of the CBFb gene at 16q22 and the MYH11 gene at 16p13, creating the novel chimeric protein CBFb-MYH11. To understand the underlying molecular mechanisms unique to M4Eo biology, we determined the gene expression profile of M4Eo cases by using cDNA and long oligonucleotide microarrays. Cases of acute myelomonocytic leukemia without CBFb-MYH11 (M4) acted as our control. We found that in the gene expression profile of M4Eo, NF-jB activators and inhibitors were upregulated and downregulated, respectively, suggesting that the NF-jB signaling pathway is activated at a higher level in M4Eo than in acute myelomonocytic leukemia M4. In addition, the gene expression profile of M4Eo indicates high cell proliferation and low apoptosis. We used real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping to confirm some of our microarray data. These findings most likely represent the functional consequences of the abnormal chimeric protein CBFb-MYH11, which is unique to this disease, and suggest that NF-jB is a potential therapeutic target for treating M4Eo patients.

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T‐cell receptor signaling induces proximal Runx1 transactivation via a calcineurin–NFAT pathway

et al. 2014

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Runx1 transcription factor is a key player in the development and function of T cells.Runx1 transcripts consist of two closely related isoforms (proximal and distal Runx1) whose expressions are regulated by different promoters. Which Runx1 isoform is expressed appears to be tightly regulated. The regulatory mechanism for differential transcription is, however, not fully understood. In this study, we investigated the regulation of the proximal Runx1 promoter in T cells. We showed that proximal Runx1 was expressed at a low level in naïve T cells from C57BL/6 mice, but its expression was remarkably induced upon T-cell activation. In the promoter of proximal Runx1, a highly conserved region was identified which spans from −412 to the transcription start site and harbors a NFAT binding site. In a luciferase reporter assay, this region was found to be responsive to T-cell activation through Lck and calcineurin pathways. Mutagenesis studies and chromatin immunoprecipitation assay indicated that the NFAT site was essential for NFAT binding and transactivation of the proximal Runx1 promoter. Furthermore, TCR signalinginduced expression of proximal Runx1 was blocked by treatment of cells with cyclosporin A. Together, these results demonstrate that the calcineurin-NFAT pathway regulates proximal Runx1 transcription upon TCR stimulation. Keywords: Cellular activation r Naive cells r T cells r TCR r Transcription factorsAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionIn T cells, engagement of the T-cell receptor (TCR) with the peptide-major histocompatibility complex on antigen-presenting Correspondence: Dr. Won Fen Wong e-mail: wonfen@um.edu.my cells recruits various molecules to the contact site, triggers a signaling cascade, induces cytokine expression, and eventually determines cell fate: differentiation, proliferation, anergy, or apoptosis [1]. TCR activation causes phosphorylation of Lck kinase whose signal is transmitted through several downstream signaling pathways to transcription factors in the nucleus. The calcineurin pathway is one of such pathways. Calcineurin dephosphorylates cytoplasmic nuclear factor of activated T-cell (NFAT) transcription C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 894-904 Leukocyte signaling 895 factor, which is then translocated into the nucleus [1] resulting in the expression of various genes including interleukin-2 (IL-2) [2]. The Runx1 transcription factor is one of the key players in T-cell functions. Runx1 is abundantly expressed in thymus and spleen [3] and plays important roles in multiple stages of T-cell development as well as the differentiation of T helper (Th) cell subsets through the interplay with other transcription factors [4]. In thymus, Runx1 cooperates with LEF-1, Ets, or c-myb to form an enhanceosome complex that activates TCRs and MHC class I gene expression [5,6]. Interestingly, on one hand, Runx1 deficiency impairs transition of double ...

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The PEBP2β/CBFβ-SMMHC chimeric protein is localized both in the cell membrane and nuclear subfractions of leukemic cells carrying chromosomal inversion 16

Abstract: The chromosomal inversion (16)(p13q22), which is associated with the M4-eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two distinct genes

Cited by 18 publications

References 33 publications

Overexpression of AML1 Transcription Factor Drives Thymocytes into the CD8 Single-Positive Lineage

Overexpression of AML1 Transcription Factor Drives Thymocytes into the CD8 Single-Positive Lineage

Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping

T‐cell receptor signaling induces proximal Runx1 transactivation via a calcineurin–NFAT pathway

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