Whole Genome Sequencing, Whole Transcriptome Sequencing Are Promising Tools for Characterizing AML and ALL Subgroups

In acute myeloid leukemia (AML), whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) provide a basis for targeted treatment selection, according to new data presented at the American Society of Hematology’s 2021 Annual Meeting.

To evaluate the accuracy of WGS and WTS in determining diagnostic subgroups in AML, researchers from the Munich Leukemia Laboratory in Germany used a NovaSeq instrument to perform WGS and WTS for a cohort of 738 patients with AML, 293 with B-cell precursor acute lymphoblastic leukemia (ALL), and 124 with T-cell ALL. 

As a result, the researchers found that WGS and WTS detected all chromosomal and molecular abnormalities that had been identified by chromosome banding analysis (CBA), and targeted panel sequencing was useful in stratifying leukemia and making a leukemia prognosis. 

Moreover, WGS outperformed CBA when in-vitro proliferation was insufficient and, in 12 cases, identified 36 chromosome aberrations that were not evaluable by CBA. The impact of WGS’s independence of in-vitro cell proliferation was most significant in patients with ALL; although 40 patients with T-ALL had a normal karyotype by CBA, WGS detected structural variants in 16% and copy number alterations in 50% of these patients.

Evaluating WGS data for 121 genes often mutated in blood cancers identified an average of 2 additional mutations per sample (range, 0-9) that could qualify as therapeutic targets.

“WGS and WTS provide all necessary genetic information to accurately determine the diagnostic and prognostic subgroup according to [World Health Organization] and [European LeukemiaNet] guidelines in AML and ALL,” the researchers concluded. “Both can be implemented with automated analysis pipelines, consequently reducing time and error rates.”

—Ellen Kurek


Haferlach C, Wencke W, Meggendorfer M, et al. Benchmarking of whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) as diagnostic tools for the genetic characterization of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in adults. Paper presented at: American Society of Hematology 2021 Annual Meeting; Atlanta, Georgia; December 11-14, 2021.