| Title |
Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma: clinical significance and inhibitory effect of rituximab
|
|---|---|
| Published in |
Annals of Hematology, May 2013
|
| DOI | 10.1007/s00277-013-1770-9 |
| Pubmed ID | |
| Authors |
Zi-Zhen Xu, Zu-Guang Xia, Ai-Hua Wang, Wen-Fang Wang, Zhi-Yin Liu, Li-Yun Chen, Jun-Min Li |
| Abstract |
Diffuse large B cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma and accounts for approximately 30% of newly diagnosed lymphoid neoplasms in Western countries, and 40-50% in China. A better understanding of the biology of DLBCL is needed for the development of potential therapeutic agents that target specific intracellular pathways. In this study, expression of the important components of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway and their clinical significance were investigated in 73 DLBCL cases. The effect of rituximab alone or combined with the PI3K/AKT/mTOR pathway inhibitor rapamycin was further evaluated in the DLBCL cell lines. A total of 73 patients were identified, including 45 men and 28 women aged 18 to 78 years (median age 50 years). Of these patients, p-AKT was positive in 40 cases (54.8%), p-p70S6K in 34 cases (46.6%), and p-4E-BP1 in 33 cases (45.2%). Activation of the PI3K/AKT/mTOR pathway was related to poor disease outcome in DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) but not in those treated with rituximab-CHOP. Rituximab combined with rapamycin synergically downregulated the PI3K/AKT/mTOR signaling pathway. Western blot analysis revealed a baseline activation status of the PI3K/AKT/mTOR pathway in DLBCL cell lines, with high levels of p-AKT, p-mTOR, in addition to downstream molecules p-p70S6K and p-4E-BP1. The results indicate that the PI3K/AKT/mTOR pathway is a potentially important signaling route and an unfavorable prognostic factor for DLBCL. Patients with PI3K/AKT/mTOR activation experience a more rapidly deteriorating clinical course with poor treatment response and decreased survival time. Addition of rituximab could downregulate PI3K/AKT/mTOR activation, reversing its negative effect on chemotherapy-treated patients. In addition, our results indicate that the combination of rituximab and inhibition of the activated PI3K/AKT/mTOR pathway could be a promising target for DLBCL therapeutic intervention in the future. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Unknown | 35 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 19% |
| Student > Master | 6 | 17% |
| Student > Ph. D. Student | 5 | 14% |
| Student > Bachelor | 2 | 6% |
| Student > Postgraduate | 2 | 6% |
| Other | 6 | 17% |
| Unknown | 8 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 22% |
| Agricultural and Biological Sciences | 6 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Immunology and Microbiology | 2 | 6% |
| Other | 5 | 14% |
| Unknown | 10 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 November 2023.
All research outputs
#7,123,837
of 23,269,984 outputs
Outputs from Annals of Hematology
#396
of 2,221 outputs
Outputs of similar age
#59,451
of 193,914 outputs
Outputs of similar age from Annals of Hematology
#3
of 28 outputs
Altmetric has tracked 23,269,984 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 2,221 research outputs from this source. They receive a mean Attention Score of 4.1. This one has done well, scoring higher than 81% of its peers.
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We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.