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Introduction: Focus on leukemia.
When stjude talks about leukemia, he thinks of the most impressive Korean drama "Blue Life and Death" in his youth, or the touching movie "I am not the God of Medicine" in the past two years, or a certain college student who is often seen diagnosed with leukemia Deeds of fighting against illness.
Most people have learned about leukemia from the plot or the news: it is a very serious and terminal illness that is "deadly"! Leukemia is a collective term for a group of cancer types.
Although people knew the existence of this blood disease as early as the 4th century BC, it was not until 1845 that John Hughes Benett officially diagnosed it in Edinburgh.
disease.
Later in the 19th century, several European doctors noticed that many of their patients had abnormally high levels of white blood cells, called leukemia.
Leukemias are mainly divided into four types: acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia.
They usually occur in the bone marrow and cause a large number of abnormal white blood cells.
Symptoms may include bleeding and ecchymosis, fatigue, and Increased risk of infection.
Without treatment, the average survival period is only 3 months.
After treatment, most patients can get remission, and the cure rate of some acute lymphoblastic leukemia can reach 90%, but the overall survival rate is still relatively low.
The blood of ordinary people and leukemia patients.
formuladrugs According to the latest global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization in 2020, there are 9.
96 million cancer deaths worldwide, of which the number of leukemia deaths exceeds 300,000, while the number of leukemia deaths in my country Reached 60,000.
Global cancer deaths.
IARC China cancer deaths.
IARC "China Poor Leukemia Children's Survival Status Survey Report" shows that leukemia is a disease that requires long-term treatment, which generally takes 2-3 years and requires 100,000-300,000 , The cost of bone marrow transplantation is 300,000-1 million. For children with leukemia, some lymphomas and other tumors, the treatment cycle is in years, and it takes 2-3 years, during which multiple hospitalizations are required.
Therefore, the treatment of leukemia requires strong economic support.
Although several new drugs for the disease have been introduced in recent years, none of them have significantly changed the treatment effect or survival rate of patients.
Fortunately, in March of this year, Dr.
Chi Wai Eric So, Professor of Leukemia Biology and Chairman, King’s College London, published a study in Science Translational Medicine through the use of highly purified human hematopoietic stem cells for prospective disease modeling and primary patients A review of the leukemia stem cells (LSCs) in the sample revealed that human hematopoietic stem cells (HSCs) and common bone marrow progenitor cells (CMPs) are two types of human acute myeloid leukemia (MLL-AML) driven by the fusion of mixed-lineage leukemia (MLL) genes.
Kind of different origins.
And use the anti-diarrhea drug fidaxomycin to reduce chemotherapy resistance.
Human HSC and CMP, but not LMPP or GMP, are the cellular targets of MLL fusion-mediated transformation.
Functional reconstruction of human AML reveals stem cell origin and vulnerability of treatment-resistant MLL-rearranged leukemia.
DOI: 10.
1126/scitranslmed.
abc4822 Study through shRNA-mediated knockout or use the small molecule inhibitor Feidamycin (currently used for Bacterial infection-related diarrhea) inhibit ABCC3, effectively sensitizing HSC-derived MLL-AML to standard chemotherapy drugs.
The study not only functionally established the two unique origins of human LSCs to MLL-AML and its role in mediating chemotherapy resistance, but also re-used a well-tolerated anti-diarrhea that has been used clinically.
Drugs have identified a potential treatment route for stem cell-related treatment resistance. In fact, recent advances in the treatment of leukemia drugs have been rapid.
In December last year, the results of a global trial at 148 locations in 23 countries led by the Monash University Mission in Australia showed that the survival rate of patients with acute myeloid leukemia (AML) increased by 30%, significantly improving the survival rate of elderly patients over 55 years of age.
Survival rate, the results of the study are published on NEJM.
Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.
DOI: 10.
1056/NEJMoa2004444 This study conducted a phase 3 azacitidine oral formulation (CC-486), a randomized, double-blind, placebo-controlled trial with 472 patients randomly assigned The primary endpoint of receiving CC-486 (300 mg) or placebo is overall survival, and secondary endpoints include relapse-free survival and health-related quality of life.
Treatment endpoint results.
DOI: 10.
1056/NEJMoa2004444 The results showed that compared with placebo, the median overall survival after randomization of CC-486 was significantly longer (P <0.
001).
The median recurrence-free survival of CC-486 was also significantly longer than that of the placebo group (P <0.
001).
In most subgroups defined based on baseline characteristics, CC-486 showed the advantages of overall survival and recurrence-free survival.
The most common adverse events in the two groups were grade 1 or 2 gastrointestinal events.
Common grade 3 or 4 adverse events were neutropenia (41% in the CC-486 group and 24% in the placebo group) and thrombocytopenia (22% and 21%, respectively).
During CC-486 treatment, the overall health-related quality of life is preserved.
This study can be described as a landmark achievement in the history of leukemia treatment.
It is well known that after intensive chemotherapy, many elderly patients cannot receive stem cell transplantation, and the risk of AML recurrence is high.
The advent of the drug can significantly delay the recurrence of the disease, thereby prolonging the survival period without affecting the quality of life.
inews.
gtimg For the treatment of leukemia, the medical science community is still in the stage of continuous exploration.
In recent years, many scholars have successively discovered new solutions for the treatment of leukemia.
Leukemia contains complex and diverse subtypes, and there is still room for exploration in its treatment.
Recently, a research team led by Icahn Mount Sinai in the United States established the first cell model.
The study published in Cell Stem Cell depicts the early to late stages of acute myeloid leukemia (AML).
Evolution.
By using gene editing technology to change the genes that make cells malignant, potential therapeutic targets in the early stages of AML have been determined.
Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets.
DOI: 10.
1016 / j.
stem.
2021.
01.
011 Leukemia is produced by acquiring somatic mutations sequentially, these mutations produce successive clones Population and disease evolution models can help clarify this process and provide information for therapeutic intervention in the early stages of the disease, but its creation faces great challenges.
Therefore, the researchers combined induced pluripotent stem cell (iPSC) and CRISPR-Cas9 technology to develop a clonal evolutionary model of acute myeloid leukemia.
By gradually introducing three driver mutations, an iPSC line was generated, which captured different premalignant stages during hematopoietic differentiation, including clonal hematopoietic (CH) and myelodysplastic syndrome (MDS), which eventually led to transplantable leukemia , And summarized the characteristics of transcription and chromatin accessibility, mainly human MDS and AML, and reproduce the process of a normal cell transforming into a malignant cell step by step.
Dynamic changes map.
DOI: 10.
1016 / j.
stem.
2021.
01.
011 By mapping the dynamic changes of the transcriptome and chromatin landscape, the results of the study characterize the transcriptional programs that drive specific transitions between disease stages, and discover inflammation and innate immune pathways It constitutes an early target and proves that inhibitors of these pathways may be a promising treatment for AML and myelodysplastic syndromes.
In summary, with the development of medicine, leukemia drug treatment, targeted therapy, hematopoietic stem cell transplantation and cell therapy have all made great progress.
However, for patients, once they become ill, they have a certain burden on themselves, their family, work, and the economy.
In the future, exploring new therapeutic targets, launching clinical trials of new drugs, optimizing stem cell transplantation, and developing affordable medical approaches will be the mission and direction of leukemia in the new era.
Source: Metz Medical Comprehensive Report authorized to reprint, submit articles and break the news.
Please contact Metz Medical Administrator MedSci (WeChat ID: medsci_m) for a recommended reading of 2 million people in the past 30 years.
The study tells you that eating fruits and vegetables like this can lead to longevity! Silent blinding eye disease—Glaucoma, not far from us.
For more information, please click to read the original text to download the Metz Medical APP~
When stjude talks about leukemia, he thinks of the most impressive Korean drama "Blue Life and Death" in his youth, or the touching movie "I am not the God of Medicine" in the past two years, or a certain college student who is often seen diagnosed with leukemia Deeds of fighting against illness.
Most people have learned about leukemia from the plot or the news: it is a very serious and terminal illness that is "deadly"! Leukemia is a collective term for a group of cancer types.
Although people knew the existence of this blood disease as early as the 4th century BC, it was not until 1845 that John Hughes Benett officially diagnosed it in Edinburgh.
disease.
Later in the 19th century, several European doctors noticed that many of their patients had abnormally high levels of white blood cells, called leukemia.
Leukemias are mainly divided into four types: acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia.
They usually occur in the bone marrow and cause a large number of abnormal white blood cells.
Symptoms may include bleeding and ecchymosis, fatigue, and Increased risk of infection.
Without treatment, the average survival period is only 3 months.
After treatment, most patients can get remission, and the cure rate of some acute lymphoblastic leukemia can reach 90%, but the overall survival rate is still relatively low.
The blood of ordinary people and leukemia patients.
formuladrugs According to the latest global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization in 2020, there are 9.
96 million cancer deaths worldwide, of which the number of leukemia deaths exceeds 300,000, while the number of leukemia deaths in my country Reached 60,000.
Global cancer deaths.
IARC China cancer deaths.
IARC "China Poor Leukemia Children's Survival Status Survey Report" shows that leukemia is a disease that requires long-term treatment, which generally takes 2-3 years and requires 100,000-300,000 , The cost of bone marrow transplantation is 300,000-1 million. For children with leukemia, some lymphomas and other tumors, the treatment cycle is in years, and it takes 2-3 years, during which multiple hospitalizations are required.
Therefore, the treatment of leukemia requires strong economic support.
Although several new drugs for the disease have been introduced in recent years, none of them have significantly changed the treatment effect or survival rate of patients.
Fortunately, in March of this year, Dr.
Chi Wai Eric So, Professor of Leukemia Biology and Chairman, King’s College London, published a study in Science Translational Medicine through the use of highly purified human hematopoietic stem cells for prospective disease modeling and primary patients A review of the leukemia stem cells (LSCs) in the sample revealed that human hematopoietic stem cells (HSCs) and common bone marrow progenitor cells (CMPs) are two types of human acute myeloid leukemia (MLL-AML) driven by the fusion of mixed-lineage leukemia (MLL) genes.
Kind of different origins.
And use the anti-diarrhea drug fidaxomycin to reduce chemotherapy resistance.
Human HSC and CMP, but not LMPP or GMP, are the cellular targets of MLL fusion-mediated transformation.
Functional reconstruction of human AML reveals stem cell origin and vulnerability of treatment-resistant MLL-rearranged leukemia.
DOI: 10.
1126/scitranslmed.
abc4822 Study through shRNA-mediated knockout or use the small molecule inhibitor Feidamycin (currently used for Bacterial infection-related diarrhea) inhibit ABCC3, effectively sensitizing HSC-derived MLL-AML to standard chemotherapy drugs.
The study not only functionally established the two unique origins of human LSCs to MLL-AML and its role in mediating chemotherapy resistance, but also re-used a well-tolerated anti-diarrhea that has been used clinically.
Drugs have identified a potential treatment route for stem cell-related treatment resistance. In fact, recent advances in the treatment of leukemia drugs have been rapid.
In December last year, the results of a global trial at 148 locations in 23 countries led by the Monash University Mission in Australia showed that the survival rate of patients with acute myeloid leukemia (AML) increased by 30%, significantly improving the survival rate of elderly patients over 55 years of age.
Survival rate, the results of the study are published on NEJM.
Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.
DOI: 10.
1056/NEJMoa2004444 This study conducted a phase 3 azacitidine oral formulation (CC-486), a randomized, double-blind, placebo-controlled trial with 472 patients randomly assigned The primary endpoint of receiving CC-486 (300 mg) or placebo is overall survival, and secondary endpoints include relapse-free survival and health-related quality of life.
Treatment endpoint results.
DOI: 10.
1056/NEJMoa2004444 The results showed that compared with placebo, the median overall survival after randomization of CC-486 was significantly longer (P <0.
001).
The median recurrence-free survival of CC-486 was also significantly longer than that of the placebo group (P <0.
001).
In most subgroups defined based on baseline characteristics, CC-486 showed the advantages of overall survival and recurrence-free survival.
The most common adverse events in the two groups were grade 1 or 2 gastrointestinal events.
Common grade 3 or 4 adverse events were neutropenia (41% in the CC-486 group and 24% in the placebo group) and thrombocytopenia (22% and 21%, respectively).
During CC-486 treatment, the overall health-related quality of life is preserved.
This study can be described as a landmark achievement in the history of leukemia treatment.
It is well known that after intensive chemotherapy, many elderly patients cannot receive stem cell transplantation, and the risk of AML recurrence is high.
The advent of the drug can significantly delay the recurrence of the disease, thereby prolonging the survival period without affecting the quality of life.
inews.
gtimg For the treatment of leukemia, the medical science community is still in the stage of continuous exploration.
In recent years, many scholars have successively discovered new solutions for the treatment of leukemia.
Leukemia contains complex and diverse subtypes, and there is still room for exploration in its treatment.
Recently, a research team led by Icahn Mount Sinai in the United States established the first cell model.
The study published in Cell Stem Cell depicts the early to late stages of acute myeloid leukemia (AML).
Evolution.
By using gene editing technology to change the genes that make cells malignant, potential therapeutic targets in the early stages of AML have been determined.
Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets.
DOI: 10.
1016 / j.
stem.
2021.
01.
011 Leukemia is produced by acquiring somatic mutations sequentially, these mutations produce successive clones Population and disease evolution models can help clarify this process and provide information for therapeutic intervention in the early stages of the disease, but its creation faces great challenges.
Therefore, the researchers combined induced pluripotent stem cell (iPSC) and CRISPR-Cas9 technology to develop a clonal evolutionary model of acute myeloid leukemia.
By gradually introducing three driver mutations, an iPSC line was generated, which captured different premalignant stages during hematopoietic differentiation, including clonal hematopoietic (CH) and myelodysplastic syndrome (MDS), which eventually led to transplantable leukemia , And summarized the characteristics of transcription and chromatin accessibility, mainly human MDS and AML, and reproduce the process of a normal cell transforming into a malignant cell step by step.
Dynamic changes map.
DOI: 10.
1016 / j.
stem.
2021.
01.
011 By mapping the dynamic changes of the transcriptome and chromatin landscape, the results of the study characterize the transcriptional programs that drive specific transitions between disease stages, and discover inflammation and innate immune pathways It constitutes an early target and proves that inhibitors of these pathways may be a promising treatment for AML and myelodysplastic syndromes.
In summary, with the development of medicine, leukemia drug treatment, targeted therapy, hematopoietic stem cell transplantation and cell therapy have all made great progress.
However, for patients, once they become ill, they have a certain burden on themselves, their family, work, and the economy.
In the future, exploring new therapeutic targets, launching clinical trials of new drugs, optimizing stem cell transplantation, and developing affordable medical approaches will be the mission and direction of leukemia in the new era.
Source: Metz Medical Comprehensive Report authorized to reprint, submit articles and break the news.
Please contact Metz Medical Administrator MedSci (WeChat ID: medsci_m) for a recommended reading of 2 million people in the past 30 years.
The study tells you that eating fruits and vegetables like this can lead to longevity! Silent blinding eye disease—Glaucoma, not far from us.
For more information, please click to read the original text to download the Metz Medical APP~
