Development of MDS in Pediatric Patients with GATA2 Deficiency: Increased Histone Trimethylation and Deregulated Apoptosis as Potential Drivers of Transformation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. In Situ Hybridization
2.3. Histological and Immunohistochemical Evaluation
2.4. Multiplex Immunofluorescence
2.5. Gene Expression Profiling
2.6. Data Analysis and Visualization
2.7. Statistical Evaluation
3. Results
3.1. Patient Characteristics
3.2. mRNA Expression of GATA2 and GATA2 Target Genes RUNX1, EZH2, IKZF1, and LYL1 Is Restored during Disease Progression in GATA2mut Patients
3.3. In GATA2 Haploinsufficient Patients, EZH2 Expression Is Increased in Hematopoietic Progenitors at Advanced Disease Stage
3.4. Robust Expression of the EZH2-Dependent H3K27me3 Gene Silencing Mark in GATA2-EB Patients
3.5. GATA2mut Patients Show Increased BCL2 Expression with Disease Progression
3.6. Profiling of BCL2 Family Members Reveals an Increased MAC Score in GATA2-EB Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | GATA2mut n = 30 | GATA2WT n = 27 | |
---|---|---|---|
Age at onset | Years, median (range) | 13 (4–20) | 9 (2–19) |
Sex | Males, n (%) | 16 (53) | 16 (59) |
Females, n (%) | 14 (47) | 11 (41) | |
Diagnosis | RCC, n (%) | 24 (80) | 17 (63) |
MDS-EB, n (%) | 6 (20) | 10 (37) | |
Normal, n (%) | 9 (33) | 15 (56) | |
Karyotype 1 | Monosomy 7, n (%) 2 | 11 (41) | 8 (30) |
Trisomy 8, n (%) | 7 (26) | 3 (11) | |
Other 3, n (%) | 0 (0) | 1 (3) |
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Schreiber, F.; Piontek, G.; Schneider-Kimoto, Y.; Schwarz-Furlan, S.; De Vito, R.; Locatelli, F.; Gengler, C.; Yoshimi, A.; Jung, A.; Klauschen, F.; et al. Development of MDS in Pediatric Patients with GATA2 Deficiency: Increased Histone Trimethylation and Deregulated Apoptosis as Potential Drivers of Transformation. Cancers 2023, 15, 5594. https://doi.org/10.3390/cancers15235594
Schreiber F, Piontek G, Schneider-Kimoto Y, Schwarz-Furlan S, De Vito R, Locatelli F, Gengler C, Yoshimi A, Jung A, Klauschen F, et al. Development of MDS in Pediatric Patients with GATA2 Deficiency: Increased Histone Trimethylation and Deregulated Apoptosis as Potential Drivers of Transformation. Cancers. 2023; 15(23):5594. https://doi.org/10.3390/cancers15235594
Chicago/Turabian StyleSchreiber, Franziska, Guido Piontek, Yuki Schneider-Kimoto, Stephan Schwarz-Furlan, Rita De Vito, Franco Locatelli, Carole Gengler, Ayami Yoshimi, Andreas Jung, Frederick Klauschen, and et al. 2023. "Development of MDS in Pediatric Patients with GATA2 Deficiency: Increased Histone Trimethylation and Deregulated Apoptosis as Potential Drivers of Transformation" Cancers 15, no. 23: 5594. https://doi.org/10.3390/cancers15235594