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Clinical Trial
. 2021 Jun 16;11(6):112.
doi: 10.1038/s41408-021-00504-5.

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center

Xue Chen  1 , Fang Wang  1 , Yang Zhang  1 , Xiaoli Ma  1 , Panxiang Cao  1 , Lili Yuan  1 , Lan Wang  1 , Jiaqi Chen  1 , Xiaosu Zhou  2 , Qisheng Wu  3 , Ming Liu  1 , David Jin  2 , Hongxing Liu  4   5   6
Affiliations
Clinical Trial

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center

Xue Chen et al. Blood Cancer J. .

Abstract

Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Tier A, B, and C fusion genes (FGs) detected in the 1000 acute leukemia cases.
a Tier A, B, and C FGs were identified in 618 samples. Most of them showed 1 fusion event (n = 508), 90 patients harbored 2 fusions, and 16 patients had 3 fusions. Only 3 patients had 4 fusions and 1 patient had 5 fusions. b Venn diagram represented the pathogenicity evaluation of the FGs found in the 618 cases. c A total of 57 distinct recurrent FGs were identified, including 39 tier A, 16 tier B, and 2 tier C FGs, respectively. Fourteen FGs had incidences higher than 1%.
Fig. 2
Fig. 2. Fusion gene networks in AML, B-ALL, T-ALL, and MPAL.
a Fusion gene network in AML. b Fusion gene network in B-ALL. c Fusion gene network in T-ALL. d Fusion gene network in MPAL. The blue and orange nodes represent the 5′ fusion gene partner and the 3′ fusion gene partner, respectively. Lines represent fusions. The size of nodes and thickness of lines reflect the frequency of the observed fusions.
Fig. 3
Fig. 3. An overview of protein kinase fusions in acute leukemia.
a Bar plots show the fraction of protein kinase fusions relative to the total number of fusion genes per leukemia subtype. b Protein kinase genes with multiple partners. c The landscape of protein kinase fusions in different leukemia subtypes. The horizontal and vertical axes represent the patients and kinase genes, respectively. Genes were ordered based on kinase family annotation. Color bar depicts the diagnosis of each sample.
Fig. 4
Fig. 4. The landscape of transcription factor fusions in different leukemia subtypes.
The horizontal and vertical axes represent the patients and transcription factor genes, respectively. Genes were ordered based on transcription factor class. Color bar depicts the diagnosis of each sample.
Fig. 5
Fig. 5. The landscape of chromatin modifier fusions in different leukemia subtypes.
The horizontal and vertical axes represent the patients and chromatin modifier genes, respectively. Genes were ordered based on chromatin modifier class. Color bar depicts the diagnosis of each sample.
Fig. 6
Fig. 6. Novel fusion genes detected in AML, B-ALL, T-ALL, and T-ALL.
The plot was generated by Circos. The outside circle indicates the chromosomal location of the unique fusion genes. The arcs indicate novel fusions in AML (a), B-ALL (b), T-ALL (c), and MPAL (d). The width of the connecting arcs reflects the recurrence of the fusion genes. Different colors of the ribbons indicate tier A (red), tier B (orange), and tier C (green) fusion genes.
Fig. 7
Fig. 7. Pie chart represented the comparison of results between whole transcriptome sequencing and fusion genes screening.
WTS whole transcriptome sequencing, FG fusion gene.
See this image and copyright information in PMC

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References

    1. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology. 2000;36:69–86. doi: 10.1046/j.1365-2559.2000.00895.x. - DOI - PubMed
    1. Chen X, Wang F, Zhang Y, Wang M, Tian W, Teng W, et al. Retrospective analysis of 36 fusion genes in 2479 Chinese patients of de novo acute lymphoblastic leukemia. Leuk Res. 2018;72:99–104. doi: 10.1016/j.leukres.2018.08.009. - DOI - PubMed
    1. Chen X, Wang F, Zhang Y, Wang M, Tian W, Teng W, et al. Panoramic view of common fusion genes in a large cohort of Chinese de novo acute myeloid leukemia patients. Leuk Lymphoma. 2019;60:1071–8. doi: 10.1080/10428194.2018.1516876. - DOI - PubMed
    1. Hirabayashi S, Ohki K, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, et al. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. Haematologica. 2017;102:118–29. doi: 10.3324/haematol.2016.151035. - DOI - PMC - PubMed
    1. Ohki K, Kiyokawa N, Saito Y, Hirabayashi S, Nakabayashi K, Ichikawa H, et al. Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion. Haematologica. 2019;104:128–37. doi: 10.3324/haematol.2017.186320. - DOI - PMC - PubMed

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