05 February 2024

RNA sequencing is a promising and clinically applicable technology for improving diagnosis and treatment of paediatric B-acute lymphoblastic leukaemia (B-ALL), researchers have reported.

The study of RNA sequencing (RNA-Seq) by researchers at the Children’s Hospital Los Angeles, and the City of Hope institute, California has been published in The Journal of Molecular Diagnostics.

In a pilot study, researchers studied archival clinical, morphologic, immunophenotypic and molecular data alongside residual DNA, RNA, frozen bone marrow aspirate and leukaemic peripheral blood samples in a group of 76 paediatric patients treated between 2016 and 2020. They then studied results from a further 86 new patients.

Dr Zhaohui Gu, from City of Hope, said: “The study showed that B-ALL cases with known subtypes by current standard of care testing were fully concordant with the RNA-Seq–based classification.

“In addition, RNA-Seq analysis allowed us to successfully classify a large proportion of cases that remained unknown upon comprehensive current standard of care testing. RNA-Seq–based classification was relatively easy to implement in a medium-size academic laboratory using data from a clinically validated fusion assay.”

Fellow researcher Dr Gordan Raca, from the children’s hospital, said: “The study showed that expression-profile-based classification, which to date has been mostly used in research, can also be a very powerful clinical assay for paediatric B-ALL. As a single test, it allows subtype determination in a higher proportion of cases than comprehensive multi-modal current standard of care testing performed at our institution.

“Therefore, it has the potential to increase both diagnostic yield and efficiency of B-ALL testing.”

Dr Raca added: “RNA-Seq analysis enables accurate determination of the genetic subtype for an increased proportion of paediatric B-ALL cases, which will allow more accurate risk stratification and optimisation of patient management. Accurate subtype determination at diagnosis will also grow our knowledge about morphologic, immunophenotypic, and clinical characteristics of novel B-ALL subtypes. We were surprised by a relatively high frequency of some novel B-ALL subtypes (like PAX5Alt and DUX4) in our patient cohort, which remain undiagnosed by current standard of care testing. The study also resulted in discovery of several previously unreported fusions.”

In an accompanying editorial in the journal, Dr Shawn Lee, from the National University of Singapore, issued a note of caution.

Dr Lee said: “Overall, RNA-seq as a single somatic genomic ALL diagnostic platform holds immense promise, although still with associated gaps. In some cases, validation of positive cases by an alternative method (such as oncogene fusion test and DNA sequencing) may still be arguably a sounder approach. The test needs further refining to comprehensively obtain mutation information beyond that of molecular subtyping to make it globally accessible.”


Hu Z, Kovach AE, Yellapantula V, Ostrow D, Doan A, Ji J, Schmidt RJ, Gu Z, Bhojwani D, Raca G. (2024) “Transcriptome Sequencing Allows Comprehensive Genomic Characterization of Pediatric B-Acute Lymphoblastic Leukemia in an Academic Clinical Laboratory.” Journal of Molecular Diagnostics, doi: 10.1016/j.jmoldx.2023.09.013

Link: https://www.jmdjournal.org/article/S1525-1578(23)00265-9/fulltext

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