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. 2021 Dec 14;5(23):4963-4968.
doi: 10.1182/bloodadvances.2021004965.

CBFB-MYH11 fusion transcripts distinguish acute myeloid leukemias with distinct molecular landscapes and outcomes

Benjamin J Huang  1   2 , Jenny L Smith  3 , Yi-Cheng Wang  4 , Kassra Taghizadeh  3 , Amanda R Leonti  3 , Rhonda E Ries  3 , Yanling Liu  5 , Pandurang Kolekar  5 , Katherine Tarlock  3   6 , Robert Gerbing  4 , Erin Crowgey  7 , Scott N Furlan  3   6 , Timothy I Shaw  5 , Kohei Hagiwara  5 , Lisa Wei  8 , Todd M Cooper  6 , Alan S Gamis  9 , Richard Aplenc  10 , E Anders Kolb  7 , Jason E Farrar  11 , Timothy Triche  12 , Todd A Alonzo  13 , Xiaotu Ma  5 , Soheil Meshinchi  3   6
Affiliations

CBFB-MYH11 fusion transcripts distinguish acute myeloid leukemias with distinct molecular landscapes and outcomes

Benjamin J Huang et al. Blood Adv. .

Abstract

  1. CBFB-MYH11 transcripts and KIT mutations predict relapse in AML.

  2. High-risk CBFB-MYH11 transcripts are associated with distinct transcriptional landscapes and upregulation of early hematopoiesis genes.

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Figures

Figure 1.
Figure 1.
CBFB-MYH11 fusion transcript subtype predicts relapse in AML. (A) CBFB-MYH11 fusion transcripts within our cohort with line weights that correspond to the associated prevalence. (B) Kaplan-Meier estimates for the probability of EFS, OS, and RR in patients with CBFB-MYH11 AML stratified based on fusion transcript (E5-E33 vs all others). (C) Oncoplot with associated somatic driver mutations based on fusion transcript status. KIT mutations are more prevalent in E5-E33 CBFB-MYH11 AMLs compared with others (Fisher’s exact test, P value = .0003). (D) Kaplan-Meier estimates for the probability of EFS, OS, and RR in patients with CBFB-MYH11 AML stratified based on fusion transcript and E17 KIT mutation status. (E) Age distribution comparing Schwind et al (adults) and patients from our cohort (pediatrics).
Figure 2.
Figure 2.
CBFB-MYH11 fusion transcript subtypes are associated with distinct transcriptional landscapes. (A) GSEA comparing E5-E33 CBFB-MYH11 AMLs with all others, using gene sets available through the Molecular Signature Database (hallmark, curated, and oncogenic signature gene sets). Three gene sets that define CBFB-MYH11 transcriptional signatures are significantly enriched in E5-E33 CBFB-MYH11 AMLs. Specifically, the Ross et al gene set is associated with a normalized enrichment score of 2.42 (P value <.0001) with the displayed heatmap of enriched genes. (B) UMAP analysis revealed that E5-E33 CBFB-MYH11 AMLs occupy a different cluster than most other CBFB-MYH11 AMLs. (C) GSEA comparing E5-E33 CBFB-MYH11 AMLs with all others and using a gene set derived by Mandoli et al based on CBFB-MYH11 chromatin immunoprecipitation sequencing (ChIP-seq) occupancy reveals significant enrichment (normalized enrichment score of 1.37, P value <.0001) in E5-E33 CBFB-MYH11 AMLs (100 most enriched genes shown). Violin plots of representative genes within the Mandoli et al gene set that are associated with hematopoietic stem cells or early hematopoiesis (Mann-Whitney U test).
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References

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