Transcriptome Data Analysis of 80 B ALL Patients in China

Introduction: Recently, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the 2022 International Consensus Classification (ICC) has proposed up to 26 genetically defined B cell acute lymphoblastic leukemia（B-ALL）entities and subtypes. However, several of them are hard to recognize with traditional diagnostic tests. Sequencing methods like whole genome sequencing or transcriptome analyses of B-ALL leukemia cells have been widely used in clinical studies and demonstrated effective tools that can provide comprehensive molecular profiling including driver genetic lessions as well as gene expression patterns.

Methods: Transcriptome sequencing analyses were performed for 80 retrospective B-ALL cases admitted to our medical team between October, 2020 and July, 2024. Among them, 79 were refractory or relapse（RR） even after hematopoietic stem cell transplantation（HSCT）, while only one was newly diagnosed. Testing specimens including bone marrows, blood or tissues with at least 5% leukemia cells. Oncogenic driver events of gene fusions, chromosome large scale copy number variation, and hotspot gene mutations were analyzed with an inhouse workflow. Subtypes were identified based on the gene expression profiles and characterized with those oncogenic mutations.

Results：All patients：37 females（F） and 43 males（M）, age from 2 to 70 years old.The genetic testing results show that: 15 pts were Unclassed（15/80，18.75%），M:F 7:8 with a median age of 22；7 pts were high hyperdiploid（7/80,8.75%）,M:F 4:3 with a median age of 5；3 pts were low hypodiploid（3/80,3.75%）：M:F 2:1 with a median age of 16；4 pts were KMT2A（4/80,5%）,M:F 1:3，with a median age of 53.5;9 pts were ZNF384（9/80,11.25%）,M:F 6:3, with a median age of 31；5 pts were MEF2D（5/80,6.25%）,M/F 0:5，with a median age of 30；9 pts were Ph positive（9/80,11.25%）,M:F 2:7 with a median age of 55；11 pts were Ph like（11/80,13.75%）,M:F 10:1 with a median age of 20；2 pts were ETV6-RUNX1（2/80，2.5%），M:F 1:1 with a median age of 15；7 pts were DUX4（7/80，8.75%）：F:M 2:5 with a median age of 18;2 pts were PAX5alt（2/80，2.5%）,M:F 2.0 with a median age of 26; 2 pts were PAX5 P80R（2/80，2.5%）,M:F 2.0 with a median age of 19.5; 3 pts were TCF3-PBX1（3/80，3.75%）,M:F 3.0 with a median age of 21;1pts was HLF,M,21.

Conclusions：

Our transcriptome sequencing indicate: only about 20% of B ALL pts belong to be unclassed, while remaining 80% of pts have clear molecular subtypes. This suggests that hematologists should try to perform whole genome sequencing or transcriptome analyses as much as possible when patients first diagnosis or relapse. This can help hematologists better understand diseases, also help patients achieve accurate diagnosis and obtain the best treatment. So far there are still many unknown molecular subtyping that need to be discovered and we still need further research in future.

No relevant conflicts of interest to declare.