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. 2024 May 1;109(5):1582-1587.
doi: 10.3324/haematol.2023.284115.

Deciphering the molecular complexity of the IKZF1plus genomic profile using Optical Genome Mapping

Jonathan L Lühmann  1 , Martin Zimmermann  2 , Winfried Hofmann  1 , Anke K Bergmann  1 , Anja Möricke  3 , Gunnar Cario  3 , Martin Schrappe  3 , Brigitte Schlegelberger  1 , Martin Stanulla  2 , Doris Steinemann  4
Affiliations

Deciphering the molecular complexity of the IKZF1plus genomic profile using Optical Genome Mapping

Jonathan L Lühmann et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Overview and Optical Genome Mapping results of the analyzed cohort. (A) A total of 142 patients from the AIEOP-BFM ALL 2000/2009 trials were enrolled. Conclusive results were obtained from 138 patients; 3 patients were excluded. Based on the Optical Genome Mapping (OGM) findings, 5 patients were reclassified. An established prognostic marker (high hyperdiploidy, ETV6::RUNX1 or iAMP21) was identified in 18 patients and a gene fusion was discovered in 53 patients. (B) Heatmap of OGM results of the 135 analyzed IKZF1del and IKZF1plus patients. Patients were grouped into those with a prognostic marker (high hyperdiploidy, ETV6::RUNX1, iAMP21), IKZF1del with or without gene fusion and IKZF1plus with or without gene fusion. MRD: minimal residual disease; CNV: copy number variation; HR: high risk; MR: medium risk; SR: standard risk; n/a: not available; hom. del.: homozygous deletion; het. del.: heterozygous deletion; dup.: duplication; SV: structural variant.
Figure 2.
Figure 2.
RCSD1::ABL2 fusion resulting from three distinct structural variants detected by Optical Genome Mapping. (A) Simple inversion inv(1)(q24.2q25.2) with breakpoints in RCSD1 and ABL2. Upper track: cytobands. Second track: genes. Third track: reference genome chromosome 1q24.2-q25.2. Lower track: patient maps indicating inversion with breakpoints in q24.2 and q25.2. (B) Derivative chromosome 1 containing three inversions: der(1)inv(1)(q24.2q25.2)inv(1)(q24.2q41)inv(1)(q25.2q41). Upper track: cytobands. Second track: genes (orange) and segments according to genomic breakpoints (blue). Third track: reference genome chromosome 1q24.2-q41. Fourth track: patient maps indicating inversions. The bottom track shows a schematic representation of the inverted segments. (C) Complex event comprising an ~150 kbp duplication and an ~150 kbp insertion in inverted direction: der(1)dup(1) (q25.2q25.2)ins(1;1)(q25.2;q24.2q24.2). The references for chromosome 1q25.2 (upper bar) and 1q24.2 (lower bar) are shown in green and the corresponding patient maps in light blue. The duplicated region with a breakpoint in ABL2 is depicted in orange, while the inserted segment with a breakpoint in RCSD1 is represented in gray.
Figure 3.
Figure 3.
Kaplan-Meier plots for event-free survival and relapse incidence in IKZF1del and IKZF1plus patients. (A) 5-year event-free survival (EFS) and (B) 5-year relapse incidence (CIR) of IKZF1del and IKZF1plus patients compared with 845 ALL-BFM 2000 patients with no IKZF1 deletion (IKZF1WT). (C) 5-year EFS and (D) 5-year CIR of IKZF1del and IKZF1plus patients when patients with high hyperdiploidy (HeH), ETV6::RUNX1, and iAMP21 were excluded from the analysis. (E) 5-year EFS and (F) 5-year CIR of IKZF1del and IKZF1plus patients when patients with HeH, ETV6::RUNX1, iAMP21 and gene fusions were excluded from the analysis. (G) 5-year EFS and (H) 5-year CIR of IKZF1del/plus patients (without HeH, ETV6::RUNX1, iAMP21) with a gene fusion compared to patients without a gene fusion. (I) 5-year EFS and (J) 5-year CIR for the different fusion subgroups: ABL-class, CRLF2, JAK2, PAX5, ZNF384 and other fusions.
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