Transcriptome Analysis with B-ALL and MLN-TK

Whole transcriptome sequencing (WTS) is becoming increasingly important in the routine diagnostics of leukemia. In addition to the holistic detection of fusion transcripts, transcriptome analysis also makes it possible to determine subtype-specific expression profiles for more accurate stratification of patients. Thus, according to the new WHO classification (5th edition), some subtypes can only be determined by analyzing gene expression profiles. Therefore, for both B-ALL and MLN-TK, we have included transcriptome analysis in our routine workflows and offer it accordingly.

Transcriptome Analysis with B-ALL

B-ALL is primarily classified into its subtypes genetically by determining copy number alterations of individual chromosomes or whole chromosome sets and by detecting translocations and corresponding fusion transcripts. In addition, we also know of groups where no known fusions are detectable in the patients, yet their expression profile is hardly distinguishable from that of patients with defined translocations – these include BCR::ABL1-like or ETV6::RUNX1-like B-ALL. The ability to detect fusion transcripts and create expression profiles is a strength of transcriptome analysis, which is why we have started using it to determine B-ALL subtypes. After whole transcriptome sequencing, we use an algorithm trained via machine learning that can distinguish and classify 18 different B-ALL subtypes based on their expression profiles (ALLSorts, Schmidt B et al., Blood Adv. 2022 Jul 26;6(14):4093-4097). Only the subgroups with deviating numbers of chromosomes (hyper/hypodiploid) are not reliably detected by this method. In contrast, however, other groups, such as BCR::ABL1-like, ETV6::RUNX1-like, and DUX4 rearrangements, can only be detected using such a method.

Transcriptome Analysis with MLN-TK

The newly named entity myeloid/lymphoid neoplasia with eosinophilia and tyrosine kinase gene fusion bears in its very name the diagnostic criterion of detection of a tyrosine kinase gene fusion. While the most commonly detected fusions are FIP1L1::PDGFRA, ETV6::PDGFRB, ZNF198::FGFR1, and also PCM1::JAK2, other tyrosine kinase gene fusions can also occur in rare cases. Due to its therapeutic relevance, when MLN-TK is suspected, an extended and broad-based screening – after ruling out known fusions – is recommended as part of a stepwise diagnostic process. The advantage of transcriptome analysis is being able to simultaneously determine aberrant tyrosine kinase expressions as well as rare tyrosine kinase gene fusions along with known ones. The sequence of a detected fusion can also be used to identify whether it occurred within the reading frame and whether it leads to a functional tyrosine kinase, which then serves as a potential target for corresponding inhibitors.


Transcriptome analysis is on our request form as a diagnostic method for both B-ALL and MLN-TK.

The author

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Dr. rer. nat. Manja Meggendorfer, MBA

Biologist, Dipl.
Head of Molecular genetics
Head of Research and Development

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