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Whole genome sequencing for malignant hematological tumors
Whole genome sequencing for malignant hematological tumors. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are two serious hematological malignancies, which can be called the “two mountains” in hematology treatment. About 1/3 of MDS patients can develop AML.
Although some progress has been made in the treatment of AML and MDS in recent years, including chemotherapy, supportive therapy, hematopoietic stem cell transplantation, and targeted/immunotherapy, which one is the most effective is still a major problem in clinical treatment.
In addition, the patients of these two blood diseases are mostly middle-aged and elderly people, and their age and physical condition do not allow too much “toss”. It is very important to choose an effective treatment accurately.
Recently, a study in the New England Journal of Medicine showed that using whole-genome sequencing to identify genomic changes in tumor cells can help doctors choose the best treatment options for patients with AML or MDS.
1. Whole genome sequencing, these advantages cannot be replicated!
At present, malignant hematological tumors, such as AML or MDS, have a high incidence of genomic abnormalities, and genetic testing has been widely used.
Although the rapid advancement of sequencing technology has also improved the ability to identify gene mutations, routine cytogenetic analysis is still an important part of patient diagnostic tests to determine chromosomal rearrangements.
However, cytogenetic analysis requires living cells from patients, which requires bone marrow biopsy; and there are limitations such as low sensitivity and limited resolution.
Because, in up to 20% of patients, tumor cells will not grow, or it is impossible to make a judgment by observing enough chromosomes. At the same time, there are some genetic changes that are too small to be seen through cytogenetic analysis.
And whole-gen sequencing can analyze the patient’s complete genome, and does not require living cells, and only uses a small amount of DNA samples from the patient’s cancer cells. Therefore, it is expected to overcome these limitations and even become a conventional detection method.
Compared with conventional genetic testing, whole-genome sequencing is more comprehensive and accurate!
Researchers have developed a simplified whole-genome sequencing method to sequence the entire genome and analyze the data in patient samples.
The clinical research obtained a total of 263 medullary cancer patients’ genome profiles, including 235 patients who have successfully undergone cytogenetic analysis, which can represent a wide range of genetic signs of AML and MDS.
By sequencing and analyzing these genes, the results obtained are compared with the results of cytogenetic analysis and targeted sequencing.
It was found that whole-genome sequencing can detect all chromosomal changes detected by cytogenetic analysis. More importantly, 17% of the 235 patients found other chromosomal changes, and the routine test results of some of them are still inconclusive.
2. Whole gene sequencing is expected to improve treatment outcome
Subsequently, in order to evaluate the feasibility of using whole-genome sequencing for routine clinical testing, the research team analyzed samples of 117 patients newly diagnosed with AML or MDS in the hospital and compared them with the results of routine genetic testing.
Among them, whole-genome sequencing obtained new genetic information in 24.8% of newly diagnosed patients, and included 16.2% of these 117 patients into the new risk category, which would help patients obtain more accurate and personalized solutions. Improve treatment outcome.
Currently, methods of identifying genomic changes usually involve several different tests. And whole-genome sequencing can determine the complete genetic makeup of a patient in one test, which is more accurate than traditional genetic testing.
However, the whole-genome sequencing method used in this study has a limitation in that it cannot identify small genetic changes like targeted sequencing. This limitation is expected to be overcome by more DNA sequencing.
In the near future, whole-genome sequencing can not only help patients diagnose genetic changes and improve the accuracy of treatment, but may also monitor the recurrence of cancer after treatment.
How to develop the best personalized treatment plan for AML/DMS patients?
At present, whole-genome sequencing has not been widely used in clinical practice. Although it has great advantages that other tests do not have, it still needs larger research and more clinical data to confirm that it cannot benefit patients with blood diseases in a short period of time.
In this regard, the Tumor Treatment Response Index (TRI) is a precision medicine method that combines molecular genetic testing, in vitro drug sensitivity screening (DSS) and artificial intelligence-driven bio-simulation to help such patients seize the 30-day “golden”. Time” to develop the best personalized treatment plan.
Top international academic conferences such as 2019 ASH and 2020 ASCO have announced relevant clinical studies on the use of TRI to guide clinical treatment decision-making in patients with refractory AML/MDS.
The results show that the personalized treatment plan recommended by TRI can accurately predict the patient’s response to a specific drug (or drug combination), allowing doctors to make more effective treatment decisions based on the response, avoid prescribing invalid treatment, and make some patients Able to receive allogeneic hematopoietic stem cell transplantation and achieve cure.
(source:internet, reference only)