-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature estimates that there are 5 to 20 million human T-cell leukemia virus 1 (HTLV-1) infections worldwide, of which 3-5% of carriers progress to fatal adult T-cell leukemia (ATL), with a median survival time of 2 To 6 months
.
Human T-cell leukemia virus 1 (HTLV-1) can cause adult T-cell leukemia (ATL), but its mechanism is still elusive
.
On November 19, 2021, the Yan Daoguang team of Jinan University published a research paper entitled "ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1" in Blood (IF=22) online.
Research reports that ORP4L is expressed in ATL cells, but not in normal T cells
.
ORP4L ablation completely blocked the occurrence of T cell leukemia induced by the mouse HTLV-1 oncoprotein Tax.
At the same time, the ORP4L expression in T cells was modified to cause mouse T cell leukemia, indicating the carcinogenic properties of ORP4L and the prerequisite for initiating T cell leukemia.
.
For molecular insight, the loss of miR-31 caused by HTLV-1 induces ORP4L expression in T cells
.
ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 production, leading to overactivation of AKT, NF-κB-dependent p53 inactivation, and induction of proto-oncogene expression and T cell leukemia
.
Consistently, ORP4L ablation eliminated human ATL cells in patient-derived xenograft ATL models
.
These results reveal a reasonable mechanism by which HTLV-1 leads to the degeneration of T cells, which can be used as a therapeutic target
.
There are an estimated 5 to 20 million human T-cell leukemia virus 1 (HTLV-1) infections worldwide, and 3-5% of the carriers progress to fatal adult T-cell leukemia (ATL), with a median survival time of 2 to 6 months
.
HTLV-1 directly infects peripheral T cells, and its oncoprotein Tax induces the malignant transformation of these cells
.
Tax induces PI3K-AKT signal activation and downstream NF-κB-dependent p53 inhibition, allowing cells to acquire oncogenic properties that promote malignant transformation
.
However, the initial mechanism by which HTLV-1 induces carcinogenesis is still elusive
.
Oxysterol binding protein (OSBP) related protein (ORP) has become a key mediator of non-vesicular lipid transport and phosphoinositide metabolism
.
In ORP, ORP4 is constitutively expressed in the brain, heart, and testis, but it is almost absent in other human and murine tissues
.
Due to the death of developing sperm, ORP4 knockout mice exhibit teratozoospermia
.
Early studies also showed that ORP4L can be abnormally induced in different malignant cell types and is the target of the natural antiproliferative steroidal saponin OSW-1, indicating that ORP4L is involved in controlling the growth of cancer cells
.
In addition, ORP4L is related to the survival of T-cell acute lymphoblastic leukemia (T-ALL) cells and leukemia stem cells (LSC) by mediating cellular phosphoinositide signaling
.
However, its functional role in the development of leukemia is uncertain
.
The study reported that ORP4L is expressed in ATL cells, but not in normal T cells
.
ORP4L ablation completely blocked the occurrence of T cell leukemia induced by the mouse HTLV-1 oncoprotein Tax.
At the same time, the ORP4L expression in T cells was modified to cause mouse T cell leukemia, indicating the carcinogenic properties of ORP4L and the prerequisite for initiating T cell leukemia.
.
For molecular insight, the loss of miR-31 caused by HTLV-1 induces ORP4L expression in T cells
.
ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 production, leading to overactivation of AKT, NF-κB-dependent p53 inactivation, and induction of proto-oncogene expression and T cell leukemia
.
Consistently, ORP4L ablation eliminated human ATL cells in patient-derived xenograft ATL models
.
These results reveal a reasonable mechanism by which HTLV-1 leads to the degeneration of T cells, which can be used as a therapeutic target
.
Reference message: https://ashpublications.
org/blood/article/doi/10.
1182/blood.
2021013579/482705/ORP4L-is-a-prerequisite-for-the-induction-of-T
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature estimates that there are 5 to 20 million human T-cell leukemia virus 1 (HTLV-1) infections worldwide, of which 3-5% of carriers progress to fatal adult T-cell leukemia (ATL), with a median survival time of 2 To 6 months
.
Human T-cell leukemia virus 1 (HTLV-1) can cause adult T-cell leukemia (ATL), but its mechanism is still elusive
.
On November 19, 2021, the Yan Daoguang team of Jinan University published a research paper entitled "ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1" in Blood (IF=22) online.
Research reports that ORP4L is expressed in ATL cells, but not in normal T cells
.
ORP4L ablation completely blocked the occurrence of T cell leukemia induced by the mouse HTLV-1 oncoprotein Tax.
At the same time, the ORP4L expression in T cells was modified to cause mouse T cell leukemia, indicating the carcinogenic properties of ORP4L and the prerequisite for initiating T cell leukemia.
.
For molecular insight, the loss of miR-31 caused by HTLV-1 induces ORP4L expression in T cells
.
ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 production, leading to overactivation of AKT, NF-κB-dependent p53 inactivation, and induction of proto-oncogene expression and T cell leukemia
.
Consistently, ORP4L ablation eliminated human ATL cells in patient-derived xenograft ATL models
.
These results reveal a reasonable mechanism by which HTLV-1 leads to the degeneration of T cells, which can be used as a therapeutic target
.
There are an estimated 5 to 20 million human T-cell leukemia virus 1 (HTLV-1) infections worldwide, and 3-5% of the carriers progress to fatal adult T-cell leukemia (ATL), with a median survival time of 2 to 6 months
.
HTLV-1 directly infects peripheral T cells, and its oncoprotein Tax induces the malignant transformation of these cells
.
Tax induces PI3K-AKT signal activation and downstream NF-κB-dependent p53 inhibition, allowing cells to acquire oncogenic properties that promote malignant transformation
.
However, the initial mechanism by which HTLV-1 induces carcinogenesis is still elusive
.
Oxysterol binding protein (OSBP) related protein (ORP) has become a key mediator of non-vesicular lipid transport and phosphoinositide metabolism
.
In ORP, ORP4 is constitutively expressed in the brain, heart, and testis, but it is almost absent in other human and murine tissues
.
Due to the death of developing sperm, ORP4 knockout mice exhibit teratozoospermia
.
Early studies also showed that ORP4L can be abnormally induced in different malignant cell types and is the target of the natural antiproliferative steroidal saponin OSW-1, indicating that ORP4L is involved in controlling the growth of cancer cells
.
In addition, ORP4L is related to the survival of T-cell acute lymphoblastic leukemia (T-ALL) cells and leukemia stem cells (LSC) by mediating cellular phosphoinositide signaling
.
However, its functional role in the development of leukemia is uncertain
.
The study reported that ORP4L is expressed in ATL cells, but not in normal T cells
.
ORP4L ablation completely blocked the occurrence of T cell leukemia induced by the mouse HTLV-1 oncoprotein Tax.
At the same time, the ORP4L expression in T cells was modified to cause mouse T cell leukemia, indicating the carcinogenic properties of ORP4L and the prerequisite for initiating T cell leukemia.
.
For molecular insight, the loss of miR-31 caused by HTLV-1 induces ORP4L expression in T cells
.
ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 production, leading to overactivation of AKT, NF-κB-dependent p53 inactivation, and induction of proto-oncogene expression and T cell leukemia
.
Consistently, ORP4L ablation eliminated human ATL cells in patient-derived xenograft ATL models
.
These results reveal a reasonable mechanism by which HTLV-1 leads to the degeneration of T cells, which can be used as a therapeutic target
.
Reference message: https://ashpublications.
org/blood/article/doi/10.
1182/blood.
2021013579/482705/ORP4L-is-a-prerequisite-for-the-induction-of-T
