Big coffee interview with Professor Lin Qiu: NGS promotes AML diagnosis and treatment and MRD monitoring

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disease caused by genetic abnormalities
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Intricate molecular diagnosis and minimal residual disease (MRD) monitoring are the only way to individualized and precise treatment
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The next-generation sequencing technology (NGS) facilitates AML diagnosis and treatment, prognostic stratification, recurrence detection and MRD monitoring with its high-throughput dynamic monitoring
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Yimaitong is fortunate to invite Professor Lin Qiu from Harbin Institute of Hematology and Tumor to share on the application of NGS in AML
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Yimaitong: What is the value of NGS in MRD monitoring of leukemia patients? Professor Lin Qiu MRD monitoring has very important value in AML
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With the continuous advancement of various treatments for AML, including chemotherapy, immunotherapy, targeted therapy, and hematopoietic stem cell transplantation, the efficacy of AML has gradually improved, and MRD monitoring has become more important
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Routine MRD monitoring mainly adopts RT-PCR and flow cytometry.
Both detection methods have their advantages and limitations
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The advantage of RT-PCR is that it can specifically target some molecular markers and has high sensitivity and accuracy.
However, RT-PCR can only cover about 30% of AML patients; flow cytometry can detect tumor cell surface markers MRD monitoring can cover about 90% of AML patients, but flow cytometry also has the phenomenon of some surface markers drifting, which cannot completely solve the MRD monitoring needs of AML
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The occurrence of AML is mainly related to the changes of genetic genes, not only the changes of chromosomes and fusion genes, but also the changes of mutant genes
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Changes in mutant genes are especially common in AML patients with normal karyotypes
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50% of AML patients have no fusion genes and chromosomal changes, and they have a normal karyotype
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The mutated genes of these patients determine the occurrence and development of the disease
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There are many types of mutant genes in AML.
There are hundreds of mutant genes currently known, which are divided into eight types of functional genes, which play a vital role in the occurrence and development of the disease
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NGS can simultaneously detect hundreds of mutant genes in a short period of time, and dynamically monitor changes in the development of AML related mutant genes
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Based on this feature, NGS has brought great help to clinical diagnosis, prognosis, targeted therapy, efficacy evaluation and recurrence prediction
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Therefore, currently NGS has been widely accepted by clinicians
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Although NGS has not been formally recognized by the Food and Drug Administration or the guidelines, the domestic top three hospitals and some second-tier hospitals have begun to carry out NGS, and some top three hospitals have begun to use NGS dynamic monitoring of MRD
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With the continuous development of NGS, the detection time of NGS is gradually shortened, and the sensitivity is gradually improved.
In the future, there will be more room for development in MRD monitoring of AML
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Yimaitong: What are the advantages of NGS compared with quantitative PCR and flow cytometry? The advantages of Professor Qiu Lin's quantitative PCR are its stability, sensitivity, and specificity, but its disadvantage is that it can only cover 30%-50% of AML patients
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The sensitivity of flow cytometry is also very high, but it is necessary to detect surface markers by flow cytometry
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The surface markers of 10% of AML patients will drift, especially after chemotherapy treatment, the probability of surface markers drifting is higher, which affects the monitoring of MRD
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NGS mainly detects mutated genes in patients, and can monitor hundreds of mutated genes in one tube of blood at the same time.
The sensitivity of NGS can be further improved as the sequencing depth increases
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The biggest advantage of NGS is that dozens of mutant genes related to the prognosis and recurrence of leukemia involved in the current MRD can be detected by NGS, and the relative quantitative changes of genes closely related to the patient's treatment efficacy and recurrence can be dynamically detected
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Yimaitong: In addition to MRD monitoring, what value and prospects does NGS have in the diagnosis and analysis of leukemia, prognostic evaluation, treatment guidance, and clonal evolution? Professor Lin Qiu NGS plays a vital role in the diagnosis, prognosis, treatment, efficacy evaluation and recurrence prediction of AML
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Although the current diagnosis of AML is still mainly based on morphology, flow cytometry, immunohistochemistry, and FISH detection, NGS can help in the diagnosis of AML subtypes
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For example, NGS has a guiding role in the treatment of low-risk subtypes of AML such as NPM1 and CEBPA.
For some subtypes of the normal karyotype of AML, NGS can also provide effective information
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The role of NGS in the prognosis of AML is even more significant
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Due to the complex stratification of the prognosis of AML, many factors are involved, including genetic factors, chromosomes, fusion genes, and mutant genes
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For AML patients with normal karyotype, the number, combination, VAF value, and locus of mutated genes directly affect the prognosis.
NGS can intuitively understand these prognostic factors of AML patients
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At present, the types of targeted drugs are gradually increasing, and FLT3 inhibitors, IDH inhibitors, TP53 inhibitors, and JAK2 inhibitors are gradually being widely used in AML
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NGS plays a vital role in targeted therapy
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NGS can not only provide detection for these targets, but also dynamically monitor the relationship between these targets and the efficacy
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Due to the high heterogeneity of AML, some patients with fusion genes may also be accompanied by multiple mutant genes.
The interaction between fusion genes and mutant genes will also play a key role in the prognosis and recurrence of AML patients
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Regardless of whether there are ETO-positive markers, some ETO-positive AML patients may cause disease recurrence due to the influence of the mutated gene
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And NGS can provide this part of patients with key and effective information for recurrence prediction
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In addition to the above advantages, NGS is currently facing some challenges
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At present, there are still many problems with NGS in terms of price, medical insurance entry, registration certificate approval, detection time, sensitivity, PCR error, and report interpretation.
These problems also restrict the application of NGS in the diagnosis and treatment of AML
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However, I believe that with the advancement of NGS technology and the improvement of the national economic level, NGS has the hope of obtaining registration certificates and entering medical insurance in the future, which will bring benefits to the majority of AML patients and clinicians
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Professor Qiu Lin, deputy director and researcher, Harbin Institute of Hematology and Oncology, member of the Hematology Branch of the Chinese Medical Association Standing Director of the Chinese Society of Clinical Oncology (CSCO) Standing Committee Member of the Chinese Society of Anticancer Society of Hematology (CSCO) Member of the Standing Committee of CSCO Leukemia Alliance Chinese Medical Association Pathophysiology Branch Member of Experimental Hematology Committee Member of the Geriatric Oncology Committee of the Chinese Society of Gerontology