Editor’s Note: From July 11 to 13, 2025, the 9th Annual Hematologic Oncology Congress of the Chinese Society of Clinical Oncology (CSCO) was held in Harbin. The event brought together top experts from China and abroad to discuss key issues in hematologic malignancies, including leukemia, lymphoma, and multiple myeloma. Topics spanned basic research, innovative drug development, precision medicine, and clinical translation. At the congress, Professor Minghui Duan from Peking Union Medical College Hospital delivered a compelling presentation titled “Key Considerations and Value of Genetic Testing in Hematologic Malignancies.” In an exclusive interview with Oncology Frontier – Hematology Frontier, Professor Duan elaborated on the critical role and latest advances of genetic testing in the diagnosis and treatment of blood cancers, offering valuable guidance for clinical practice.Oncology Frontier – Hematology Frontier: In recent years, genetic testing has been increasingly applied in hematologic malignancies. Could you share your thoughts on the core value of genetic testing in the diagnosis and classification of these diseases?
Professor Minghui Duan: Genetic testing is absolutely essential in the management of hematologic malignancies. To date, we believe that all cancers are likely driven by genetic alterations. If we have not yet identified specific genetic drivers in certain cases, it is probably due to current technological limitations. Future research must focus on uncovering the underlying driver genes across various tumor types. As we deepen our understanding of these mechanisms, we’ll be able to offer more precise diagnoses.
The primary value of genetic testing lies in diagnosis and differential diagnosis. Through genomic analysis, we can clearly distinguish between diseases that may appear similar on the surface, enabling more accurate classification and identification. Once specific driver genes are identified, genetic testing also plays a crucial role in drug development. By studying gene structures in detail, we can design highly specific targeted therapies that intervene directly at the molecular level to disrupt tumor development and progression. A classic example is the use of imatinib in chronic myeloid leukemia, which exemplifies successful gene-driven therapy.
Moreover, genetic testing allows for quantitative assessment of tumor burden. By tracking the level of gene expression or mutation load, we can evaluate treatment response. A decline in these values indicates tumor regression, while an increase suggests disease progression. Thus, genetic quantification is an important marker for monitoring therapeutic efficacy in hematologic cancers.
Importantly, emerging research suggests that hematologic malignancies driven by genetic mutations may be controllable through targeted therapy that reduces tumor burden to extremely low levels, potentially allowing the immune system to recover and maintain disease control without relapse. This concept has already shown promise in the treatment of chronic myeloid leukemia and may be validated in other tumor types in the future. Consequently, quantitative genetic testing may not only serve as a tool for response assessment but also play a pivotal role in determining whether patients are eligible for treatment discontinuation and potentially considered cured.
In summary, genetic testing is indispensable across all stages of hematologic cancer care—from initial diagnosis to disease control. Clinicians should tailor the choice of genetic testing method based on the patient’s condition, disease subtype, and phase of treatment to obtain the most accurate and clinically relevant information.
Oncology Frontier – Hematology Frontier: In the treatment of hematologic malignancies, how does genetic testing support clinicians in developing personalized therapeutic strategies? Could you share any successful examples or experiences from Peking Union Medical College Hospital?
Professor Minghui Duan: Genetic testing plays a crucial role in guiding treatment selection. Take chronic myeloid leukemia (CML) as an example: if a patient tests positive for the BCR-ABL fusion gene, several targeted therapies are available. However, if further testing reveals ABL kinase domain mutations—particularly specific mutations within the fusion gene—treatment strategies must be adjusted accordingly. For instance, the T315I mutation renders common tyrosine kinase inhibitors (TKIs) like imatinib, nilotinib, and dasatinib ineffective. In such cases, alternative agents such as olverembatinib or asciminib should be considered. This demonstrates how genetic profiling provides clinicians with precise information for treatment decision-making.
Another classic example is diffuse large B-cell lymphoma (DLBCL). While all patients may initially receive the same diagnosis under standard pathology, molecular genetic profiling can further stratify them into subtypes such as MCD and BN2. Each subtype requires a tailored approach based on its unique molecular characteristics. Notably, Chinese researchers, including Professor Weili Zhao’s team, have made significant progress in the molecular classification of DLBCL. Their work provides a scientific foundation for personalized therapy. For example, patients with the MCD subtype have shown improved outcomes with BTK inhibitor-based combination regimens.
In addition, TP53 mutations are a key prognostic indicator in hematologic malignancies. Whether in myeloid or lymphoid cancers, TP53 mutations are typically associated with poor prognosis. At the time of initial diagnosis, if a patient is found to have high-frequency TP53 mutations or multiple TP53 “hits,” treatment should be intensified. For instance, in myeloproliferative neoplasms, the presence of a TP53 mutation suggests the need for early allogeneic hematopoietic stem cell transplantation (allo-HSCT)—ideally within one year—to avoid delays caused by ineffective therapies. In lymphoma, TP53-mutant cases are classified as high-risk. Emerging evidence supports the early incorporation of CAR-T cell therapy in frontline treatment for these patients, in hopes of improving outcomes and long-term survival.
These examples illustrate how genetic testing informs not only the selection of targeted therapies but also the overall treatment intensity and timing, allowing clinicians to deliver personalized, effective, and timely care.
Oncology Frontier – Hematology Frontier: As genetic testing technologies continue to advance, how can we strike a balance between clinical accuracy and practical challenges such as cost and turnaround time? In your view, what is the future outlook for genetic testing in hematologic malignancies?
Professor Minghui Duan: Genetic testing, being a relatively high-cost technology, should be applied rationally at appropriate times and under appropriate circumstances. The choice of testing methodology should be guided by clinical need rather than a one-size-fits-all approach—for example, indiscriminately conducting whole-exome or whole-genome sequencing is not always necessary.
Take chronic-phase chronic myeloid leukemia (CML) as an example: in most cases, BCR-ABL testing alone is sufficient at diagnosis. There’s no theoretical need to perform broad next-generation sequencing (NGS) initially. However, if the patient shows a poor response to treatment after three months or develops unexpected hematologic toxicity, then expanding testing to include NGS may be warranted to evaluate treatment resistance or identify emerging mutations.
In some cases, NGS may reveal genetic features unrelated to the malignancy itself—such as germline variants rather than tumor-specific mutations. In these instances, further investigation through whole-exome or whole-genome sequencing may be required to clarify the underlying cause. Therefore, the selection of a genetic testing method must be tailored to the disease type, treatment phase, and clinical presentation. Blindly conducting broad panels or misinterpreting incidental findings can not only lead to incorrect treatment decisions but also waste valuable healthcare resources—placing a financial burden on both patients and the healthcare system.
In summary, genetic testing should be conducted at the right time, for the right patient population, and using the most appropriate technique. Overuse of testing can lead to unnecessary resource consumption and may even cause psychological distress—especially if the detected gene variants are of uncertain significance or not clearly pathogenic. This can heighten anxiety for patients.
Thus, the application of genetic testing must be guided by scientific rigor and clinical relevance to maximize its value in practice. Only by adhering to these principles can we ensure that genetic testing enhances care while minimizing unintended consequences for both individuals and society.
Oncology Frontier – Hematology Frontier: Does the value of genetic testing vary across different types of hematologic malignancies? In your opinion, which genetic markers are most critical for guiding treatment decisions and assessing prognosis?
Professor Minghui Duan: This is a highly complex issue, as different tumors are driven by distinct genetic alterations. For example, chronic myeloid leukemia (CML) is driven by the BCR-ABL fusion gene; in lymphomas, MYD88 mutations are a common oncogenic driver; while hairy cell leukemia is predominantly driven by the BRAF V600E mutation—which, interestingly, can also drive other conditions such as histiocytic disorders. Therefore, it’s essential to clearly understand the genetic landscape of each disease and select testing methods accordingly.
One important phenomenon is that the same gene can drive different malignancies. The BRAF V600E mutation, for instance, has been identified as a driver across a range of cancers, including thyroid cancer, lung cancer, hairy cell leukemia, melanoma, and various histiocytic diseases. In such cases, using the same targeted therapy—such as dabrafenib—can lead to similarly favorable outcomes across these disease types. Dabrafenib has demonstrated significant efficacy in treating BRAF V600E-driven hairy cell leukemia, Langerhans cell histiocytosis, lung cancer, thyroid cancer, and melanoma.
Conversely, within a single disease type, multiple distinct genetic drivers may exist. For example, diffuse large B-cell lymphoma (DLBCL) may be driven by mutations in MYD88, NOTCH2, NOTCH1, or TP53. These genetic differences not only shape the molecular profile of the disease but also have a profound impact on treatment decisions and prognosis. Therefore, even within the same diagnostic category, diverse genetic backgrounds necessitate tailored therapeutic strategies and individualized prognostic assessments.
In summary, the diversity of genetic drivers presents a significant challenge in the treatment of hematologic malignancies. To address this complexity, clinical and translational research must work hand in hand to collect and organize comprehensive genomic data and build robust genetic databases. Looking ahead, the integration of advanced artificial intelligence (AI) technologies may enable us to analyze and interpret this complex genetic information, ultimately facilitating truly precise and personalized treatment plans for each patient.
Professor Minghui Duan Peking Union Medical College Hospital
- Chief Physician, Department of Hematology, Peking Union Medical College Hospital
- Deputy Chair, First Youth Committee, Hematology Branch, Beijing Medical Association
- Member, Hematopoietic Stem Cell Application Group, Hematology Branch, Chinese Medical Association
- Vice Chair, MPN/MDS Committee, China Association for Medical Education
- Member, Expert Committee of the Chinese MDS and MPN Working Group, Hematologic Oncology Committee, Chinese Anti-Cancer Association
- Member, Anti-Leukemia Alliance Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Deputy Chair, Hematology Expert Committee, Gleevec Patient Assistance Program, China Charity Federation
- Medical Science Communication Expert, Ministry of Health’s Clinical Physician Science Outreach Program
Key Areas of Focus: Hematopoietic stem cell transplantation, lymphoma, leukemia, myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS)
Specialties: Diagnosis and treatment of complex and rare hematologic diseases
