Ann Lab Med.  2025 May;45(3):339-342. 10.3343/alm.2024.0622.

Identification of IGH::DUX4 Rearrangements Using RNA-sequencing in a Patient with ALL: A Case Report

• Lim S
• Choi YJ
• Yeom E
• Ahn WK
• Lee ST
• Choi JR
• Hahn S
• Shin S

• KMID: 2567977
• DOI: http://doi.org/10.3343/alm.2024.0622

Figure

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  Fig. 1 Morphologic and molecular characterization of B-ALL with IGH::DUX4 rearrangement, including minimal residual disease tracking. (A) Bone marrow biopsy (magnification, 1×) revealing a bone marrow packed with blasts. (B) Blasts display a high nuclear-to-cytoplasmic ratio with round nuclei and prominent nucleoli (magnification, 100×). (C) Changes in IGH and IGK clonotypes over time in response to treatment, indicating minimal residual disease. During diagnosis, clonotype frequency was presented as a percentage of total lymphocytes. At follow-up, it was adjusted to represent a percentage of total cells using LymphoQuant Internal Controls (Invivoscribe Technologies, San Diego, CA, USA). Abbreviations: CR, complete remission; IM, interim maintenance; DI, delayed intensification.

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  Fig. 2 Transcriptomic and genomic characterization of B-ALL with IGH::DUX4 rearrangement. (A) Heatmap of differentially expressed genes (DEGs) identified by edgeR. Data for this analysis were obtained from the Genomics Platform (St. Jude Cloud, https://www.stjude.cloud/) and included 16 ALL subtypes, each represented by seven randomly sampled cases. Our case data were processed into feature counts according to the St. Jude RNA-seq expression classification workflow (https://platform.stjude.cloud/workflows/rnaseq-expression-classification) and are represented as “Case” within the “Other” group, which comprises 15 ALL subtypes excluding DUX4r. Gene expression profiles were derived from a matrix of DEGs identified through edgeR analysis (https://bioconductor.org/packages/release/bioc/html/edgeR.html), with the DUX4r group compared with the “Other” group as a reference. DEGs were selected based on significantly higher or lower expression in the DUX4r group, with thresholds of |log2FC| >1 and an adjusted P<0.0001. Our case (“Case”) clustered within the DUX4r group, suggesting alignment in the expression profile with the DUX4r subtype. (B) Identification of the DUX4r breakpoint (blue arrow) within the IGHJ4 region on chromosome 14. Illustrated is an enlarged view of the DUX4r locus on chromosome 14, GRCh37 reference genome, between positions 106,324,391 and 106,334,508, viewed using Integrative Genomics Viewer (Broad Institute, Cambridge, MA, USA). Previous studies have identified that the breakpoint characteristic of the DUX4r subtype of ALL often occurs within the region between IGHJ4 and IGHD2-15 [3, 8]. Guided by these findings, we examined the genomic location of IGHJ4 (chr14: 106,322,261 – 106,332,378) and detected the presence of DUX4r at this locus.

Reference

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