Cyclin B1 is commonly expressed in the cytoplasm of primary human acute myelogenous leukemia cells and serves as a leukemia‐associated antigen associated with autoantibody response in a subset of patients

Ersvær, Elisabeth; Zhang, Jian Ying; McCormack, Emmet; Olsnes, Astrid Marta; Ånensen, Nina; Tan, Eng M.; Gjertsen, Bjørn Tore; Bruserud, Øystein

doi:10.1111/j.1600-0609.2007.00899.x

Cited by 29 publications

(30 citation statements)

References 63 publications

(96 reference statements)

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“…Finally, the histone modifier MLL is affected by the various 11q23-involving translocations; MLL functions as a cell cycle regulator through its effects on CDC45 and the function of CDC45 in cell cycle regulation seems to be altered especially in the patient subset with these translocations [102]. Table 4 gives an overview of important regulators of the G2 phase that ends up with CDC25 mediated activation of CDK1/cyclin B; the described abnormalities of G2 regulation in primary human AML cells are summarized in the table [95,[127][128][129][134][135][136][137][138][139][140]. Similar to the G1 phase, the molecular context of CDC25 varies between patients also for this phase, but in contrast to the G1 phase where the heterogeneity is mainly due to the direct effects of AML-associated genetic abnormalities, the heterogeneity of G2 regulation is mainly determined by differences in expression levels (BRCA1, PP2A, PLK1, cyclin B) or isoform profiles (p53, PP2A).…”

Section: Regulation Of the S-phasementioning

confidence: 99%

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

et al. 2014

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Abstract:The cell division cycle 25 (CDC25) phosphatases include CDC25A, CDC25B and CDC25C. These three molecules are important regulators of several steps in the cell cycle, including the activation of various cyclin-dependent kinases (CDKs). CDC25s seem to have a role in the development of several human malignancies, including acute myeloid leukemia (AML); and CDC25 inhibition is therefore considered as a possible anticancer strategy. Firstly, upregulation of CDC25A can enhance cell proliferation and the expression seems to be controlled through PI3K-Akt-mTOR signaling, a pathway possibly mediating chemoresistance in human AML. Loss of CDC25A is also important for the cell cycle arrest caused by differentiation induction of malignant hematopoietic cells. Secondly, high CDC25B expression is associated with resistance against the antiproliferative effect of PI3K-Akt-mTOR inhibitors in primary human AML cells, and inhibition of this isoform seems to reduce AML cell line proliferation through effects on NFκB and p300. Finally, CDC25C seems important for the phenotype of AML cells at least for a subset of patients. Many of the identified CDC25 inhibitors show cross-reactivity among the three CDC25 isoforms. Thus, by using such cross-reactive inhibitors it may become possible to inhibit OPEN ACCESSMolecules 2014, 19 18415 several molecular events in the regulation of cell cycle progression and even cytoplasmic signaling, including activation of several CDKs, through the use of a single drug. Such combined strategies will probably be an advantage in human cancer treatment.

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Section: Regulation Of the S-phasementioning

confidence: 99%

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

et al. 2014

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“…42 The recently described AML-related CTA cyclin A1 has also been implicated in the G1/S-phase regulation. 33 Other LAAs, including AurA, 32 cyclin B1, 45 M-phase phosphoprotein 11 (MPP11), 36 NuSAP1, 46 SSX2IP 36 and RHAMM, 36 are predominantly involved in regulating the G2/M transition or the mitotic phase of the cell cycle. AurA, NuSAP1 and RHAMM are also required for mitotic spindle stability.…”

Section: Criterion 3: Oncogenicitymentioning

confidence: 99%

“…These studies, including WT1 peptide and WT1-targeted dendritic cell vaccine trials, have unequivocally established that CD8 þ T-cell immune responses specific to WT1 can be induced by active immunization in a substantial number of AML patients. 14 In those patients, multiple WT1 CTL epitopes have been recognized as immunogenic (including WT1 [37][38][39][40][41][42][43][44][45] , WT1 [126][127][128][129][130][131][132][133][134] , WT1 [187][188][189][190][191][192][193][194][195] and WT1 [235][236][237][238][239][240][241][242][243] ), demonstrating the excellent in vivo immunostimulatory potential of WT1 (Table 1). 14,72 This is further supported by the capacity to induce WT1-specific CD4 þ helper T-cell immunity in patients with AML through active immunization.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

“…87 These findings were corroborated by the later work of Rezvani et al, 73 who observed spontaneous T-cell responses to PR1 and WT1 [126][127][128][129][130][131][132][133][134] in two out of eight patients before immunization with a combined PR1/WT1 peptide vaccine. 73 In a separate study, the same group found that such CTL responses were not limited to the immunodominant WT1 [126][127][128][129][130][131][132][133][134] epitope, but could also be directed against other HLA-A*0201-restricted WT1-derived epitopes (WT1 [37][38][39][40][41][42][43][44][45] , WT1 [187][188][189][190][191][192][193][194][195] and WT1 [235][236][237][238][239][240][241][242][243] ). 88 A similar observation was made regarding PRAME, which is known to contain at least four different HLA-A*0201-restricted epitopes that can be naturally recognized (PRA …”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

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Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.

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“…In addition, the available data show that a number of the target antigens are cellular proteins, such as p53 whose aberrant regulation or overexpression is capable of leading to tumorigenesis, as well as CyclinB1 (Crawford et al, 1982;Winter et al, 1992;Soussi, 2000;Himoto et al, 2005;Ersvaer et al, 2007). It has been also demonstrated that the immune surveillance system in certain cancer patients has the capability of recognizing these antigenic changes in cancer cells and produce autoantibodies, which can amplify the response signal to the TAAs (Tan, 2001;Tan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer

Qin

Wang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized miniarray of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.

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Cyclin B1 is commonly expressed in the cytoplasm of primary human acute myelogenous leukemia cells and serves as a leukemia‐associated antigen associated with autoantibody response in a subset of patients

Abstract: Our studies demonstrate that primary human AML cells show aberrant cytoplasmic expression of cyclin B1 for a majority of patients and a specific humoral immune response was also detected for a subset of patients with untreated leukemia.

Cited by 29 publications

References 63 publications

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer

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