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. 2024 Oct 1;109(10):3419-3425.
doi: 10.3324/haematol.2024.285410.

ASXL1/TET2 genotype-based risk stratification outperforms ASXL1 mutational impact and is independent of mutant variant allele fractions in chronic myelomonocytic leukemia

Clifford M Csizmar  1 , Mark Gurney  1 , Rashmi Kanagal-Shamanna  2 , Kelly Chien  3 , Danielle Hammond  3 , Terra L Lasho  1 , Christy M Finke  1 , Christopher Dean  1 , Anuya Natu  1 , Abhishek A Mangaonkar  1 , Aref Al-Kali  1 , Naseema Gangat  1 , Ayalew Tefferi  1 , Hassan Alkhateeb  1 , Guillermo Garcia-Manero  3 , Rami S Komrokji  4 , Najla A Ali  4 , Eric Padron  4 , Guillermo Montalban-Bravo  3 , Mrinal M Patnaik  5
Affiliations

ASXL1/TET2 genotype-based risk stratification outperforms ASXL1 mutational impact and is independent of mutant variant allele fractions in chronic myelomonocytic leukemia

Clifford M Csizmar et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Prognostic implications of ASXL1/TET2 co-mutation status in chronic myelomonocytic leukemia. (A) The upper panel (histogram) shows the distribution of cases with the indicated number of mutations in ASXL1 or TET2. The lower panel (violin plot) shows the distribution of mutational variant allele fractions (VAF) for ASXL1 in blue (median 37%, quartiles 28-45%) and TET2 in red (median 45%, quartiles 40-49%). (B) Median overall survival (mOS) and (C) acute myeloid leukemia-free survival (LFS) of the cohort stratified by ASXL1/TET2 genotype. (D) No correlation was observed between mutation VAF and either OS or LFS. P>0.39 for all correlations by both Pearson linear regression and Cox proportional hazard modeling. The mOS of the primary cohort stratified into low-, intermediate- (inter), and high-risk subgroups by the (E) Groupe Francophone des Myelodysplasies (GFM), (F) Mayo-Molecular (Mayo-Mol), and (G) CPSS-Molecular (CPSS-Mol) models each with the addition of TET2 mutation status The mOS of the external cohort stratified by the (H) GFM, (I) Mayo-Mol, and (J) CPSS-Mol models each with the addition of TET2 mutation status. In all Kaplan-Meier analyses, data are presented as median survival (95% confidence interval) in months with log-rank P values.
Figure 2.
Figure 2.
Risk restratification from existing chronic myelomonocytic leukemia prognostic models to models incorporating TET2 mutation status. Stacked colored bar plots show the restratification of existing prognostic models to the updated models incorporating TET2 mutation status for patients whom both scores could be calculated. Each bar corresponds to one existing risk category while colors represent the new risk categories with TET2 status. The gray bar plots represent the percentage of restratified patients within each contemporary model’s stratum. The pie charts depict the ASXL1/TET2 genotypes of the patients who were upstaged in each model. The addition of TET2 status to the Groupe Francophone des Myelodysplasies (GFM) model did not upstage any patients, and therefore no pie chart is depicted for this model. Inter: intermediate.
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References

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