On August 22–23, 2025, the 13th Lu Daopei Hematology Conference was held in Beijing, jointly organized by the Beijing Health Promotion Association and the Guangzhou Kapok Oncology and Rare Disease Foundation, and hosted by the Beijing Lu Daopei Hematology Institute. The conference brought together leading global experts to discuss hematopoietic stem cell transplantation, cellular therapy, and precision management of hematologic malignancies. With more than a thousand participants, it provided a high-level and in-depth academic platform. During the meeting, Professor Tong Wang of Hebei Yanda Lu Daopei Hospital delivered a presentation on “Genetic Features and Survival Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation in Multilineage-Involved BCR::ABL1-Positive B-ALL.” Oncology Frontier – Hematology News invited Professor Wang to elaborate on the study’s core findings, providing important guidance for optimizing transplant strategies.PART 1
At both the EHA meeting and this conference, you focused on multilineage-involved BCR::ABL1-positive B-ALL. Could you share the motivation and clinical background for this study? How common are these patients in clinical practice?
Professor Tong Wang: BCR::ABL1-positive B-acute lymphoblastic leukemia (B-ALL) demonstrates marked genetic heterogeneity. In both clinical and basic research, acute leukemias are further subdivided by morphology, immunophenotype, cytogenetics, and molecular biology, and these subgroups differ in therapeutic strategies and outcomes.
For the first time, the 2022 International Consensus Classification (ICC) formally divided BCR::ABL1-positive B-ALL into two molecular subtypes: one restricted to lymphoid abnormalities and one with multilineage involvement. This classification was based on clustering analysis of more than 2,800 ALL-related genes, which clearly distinguished two separate groups. An independent clustering study of over 110 cases confirmed the existence of these subtypes and even identified further subdivisions.
In the lymphoid-restricted subtype, IKZF1, CDKN2A, and PAX5 deletions are common. In contrast, the multilineage-involved subtype more often features monosomy 7 and loss of the HBS1L gene. According to published data, the multilineage-involved subtype accounts for about 30% of BCR::ABL1-positive B-ALL.
PART 2
Based on your team’s research, what are the key genetic features of multilineage-involved BCR::ABL1-positive B-ALL? How do survival outcomes look after allogeneic HSCT in this group?
Professor Tong Wang: Defined by molecular clustering, multilineage-involved BCR::ABL1-positive B-ALL is characterized by distinct genetic features. The lymphoid-restricted subtype commonly shows IKZF1, CDKN2A, and PAX5 deletions, sometimes with high hyperdiploidy or trisomy 21. By contrast, the multilineage-involved group more frequently presents with monosomy 7 and HBS1L deletions.
These subtypes also differ by age distribution: multilineage-involved cases are more common in adults. Additionally, this group shows a higher proportion of BCR-ABL P210 transcripts and a lower frequency of P190, reflecting differences in molecular expression backgrounds. Together, these findings provide an initial genetic and clinical portrait of multilineage-involved BCR::ABL1-positive B-ALL.
Clinical studies on this subtype remain limited, with relatively small patient cohorts reported. Both published data and our own center’s experience suggest that most of these patients ultimately require allogeneic HSCT. The rate of achieving deep molecular remission with tyrosine kinase inhibitor (TKI)–based regimens is relatively low, which is why transplantation becomes a preferred option. Importantly, survival outcomes after transplantation are encouraging. At our center, the three-year overall survival (OS) rate for this subtype was 69.4%, which is comparable to our overall B-ALL transplant cohort, where the five-year OS rate was about 69.9%, nearly 70%. This demonstrates that patients with multilineage-involved BCR::ABL1-positive B-ALL can achieve favorable outcomes from allogeneic HSCT.
PART 3
Given your findings, should induction therapy for newly diagnosed multilineage-involved patients be modified—for example, with intensified myeloid-directed therapy—or should transplantation be recommended directly? How do you approach the timing of transplantation in these patients?
Professor Tong Wang: At present, awareness of this newly defined molecular subtype is still limited in clinical practice. Systematic molecular classification is not yet routinely performed for newly diagnosed BCR::ABL1-positive B-ALL, which means that many multilineage-involved patients are not adequately recognized. Improving diagnostic capacity for this subtype is therefore an urgent need in order to achieve more precise and personalized therapy.
Based on our research and clinical observations, these patients can achieve complete remission, but BCR::ABL1 transcript levels often remain detectable, which may be misinterpreted as residual disease or poor response. Further analysis using cell-sorting techniques has shown that the transcript signal in some cases originates not from lymphoid blasts but from myeloid cells. Because standard B-lineage–directed chemotherapy does not eradicate these myeloid cells, the fusion gene signal persists.
Literature and our own data suggest that achieving deep molecular remission is challenging in this subtype. For this reason, allogeneic HSCT should be considered a key therapeutic option. Given that the subtype is more frequent in adults, transplantation should be pursued as early as feasible—if patient condition allows—to improve prognosis.
Expert Profile
Professor Tong Wang Hebei Yanda Lu Daopei Hospital
- Researcher in Clinical Medicine
- Director, Cytogenetics and Molecular Cytogenetics Laboratory, Lu Daopei Medical Group
- Member, Expert Committee, Hematopathology Group of the Hematologic Oncology Branch, Chinese Anti-Cancer Association
- Invited Expert, Hematology and Lymphoid Malignancy Laboratory Medicine Committee, Chinese Medical Doctor Association
- Council Member, Beijing Society of Laboratory Medicine
- Standing Committee Member, Hematology and Body Fluid Laboratory Medicine Branch, Beijing Society of Laboratory Medicine
- Member, Laboratory Medicine Committee, Chinese Association of Integrative Medicine
- Standing Member and Senior Advisor, Laboratory Medicine Branch, Bethune Spirit Research Association
- Standing Committee Member, Hematologic Laboratory Diagnostics Quality Management Group, Chinese Association of Medical Quality Management
Professor Wang has more than 30 years of experience in cytogenetics and molecular cytogenetics of hematologic malignancies. He has contributed to multiple professional textbooks, including Clinical Hematology Laboratory Medicine, and participated in drafting the Chinese Expert Consensus on Cytogenetic and Molecular Cytogenetic Diagnostics in Hematologic Malignancies. His research has been published in journals such as Cancer Gene Therapy and has been featured multiple times in abstracts and oral presentations at major international meetings including ASH, EHA, and JSH.
