Altered Expression of m6A-Associated Genes Is Linked with Poor Prognosis in Pediatric Acute Myeloid Leukemia Patients
Abstract
1. Introduction
2. Methodology
2.1. Study Population
2.2. DNA and RNA Isolation
2.3. Molecular Subtyping
2.4. Expression Level Measurement of m6A-Associated Genes
2.5. Statistical Analysis
3. Results
3.1. Clinical Characteristics of Pediatric AML Patients at Diagnosis
3.2. Expression Profile of m6A-Associated Genes in Pediatric AML Patients
3.3. Correlation of Expression Profiles of m6A-Related Genes with Various Clinicopathological Factors
3.4. Molecular Subtyping of Pediatric AML Patients for Common Mutations and Fusions
3.5. Differential Expression of m6A-Associated Genes in Different Subtypes in Pediatric AML Patients
3.6. Correlation of m6A-Related Genes with Clinical Outcome in AML Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Clinical and Hematological Parameters | AML | |
---|---|---|
Age (n = 57) | Range 1–12 years (≤5 = 33, ≥5 = 34) | Median = 7 years |
Gender (n = 57) | Male = 41; Female = 16 | Ratio (M:F) = 2.6:1 |
WBC count (×103/µL) (n = 55) | Range 300–690,000 | Median = 33,800 |
Remission post-induction course 1 (n = 46) | Positive: 36 | Negative: 10 |
Remission post-induction (n = 46) | Positive: 40 | Negative: 06 |
Percent blast count at diagnosis (n = 47) | ≤50% = 11 ≥50% = 36 | |
FAB subtype (n = 52) | M0 = 3 | |
M1 = 12 | ||
M2 = 12 | ||
M3 = 03 | ||
M4 = 12 | ||
M5 = 07 | ||
M7 = 03 | ||
Events (n = 57) | Death = 15 | |
Relapse = 15 | ||
Progressive disease = 06 |
METTL3 | p Value | METTL14 | p Value | YTHDF1 | p Value | YTHDF2 | p Value | FTO | p Value | ALKBH5 | p Value | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
+ | − | + | − | + | − | + | − | + | − | + | − | |||||||
Age (in years, n = 57) | ||||||||||||||||||
≤5 | 8 | 15 | 0.849 | 7 | 16 | 0.934 | 3 | 20 | 0.611 | 4 | 19 | 0.98 | 9 | 14 | 0.215 | 1 | 22 | 0.22 |
>5 | 11 | 23 | 10 | 24 | 3 | 31 | 6 | 28 | 19 | 15 | 0 | 34 | ||||||
Gender (Male = M, Female =F, n = 57) | ||||||||||||||||||
M | 13 | 28 | 0.677 | 13 | 28 | 0.619 | 4 | 37 | 0.762 | 7 | 34 | 0.881 | 18 | 23 | 0.207 | 1 | 40 | 0.529 |
F | 6 | 10 | 4 | 12 | 2 | 14 | 3 | 13 | 10 | 6 | 0 | 16 | ||||||
TLC (×103/µL, n = 55) | ||||||||||||||||||
<10 | 13 | 34 | 0.052 | 12 | 35 | 0.159 | 3 | 44 | 0.009 | 6 | 41 | 0.012 | 23 | 24 | 0.549 | 0 | 47 | 0.014 |
≥10 | 5 | 3 | 4 | 4 | 3 | 5 | 4 | 4 | 3 | 5 | 1 | 7 | ||||||
Remission post-course 1 (n = 46) | ||||||||||||||||||
Yes | 11 | 25 | 0.973 | 10 | 26 | 0.62 | 1 | 35 | 0.594 | 4 | 32 | 0.92 | 19 | 17 | 0.976 | 0 | 36 | - |
No | 3 | 7 | 2 | 8 | 0 | 10 | 1 | 9 | 5 | 5 | 0 | 10 | ||||||
Remission post-induction (n = 46) | ||||||||||||||||||
Yes | 12 | 28 | 0.869 | 11 | 29 | 0.573 | 1 | 39 | 0.695 | 5 | 35 | 0.359 | 21 | 19 | 0.909 | 0 | 40 | - |
No | 2 | 4 | 1 | 5 | 0 | 6 | 0 | 6 | 3 | 3 | 0 | 6 | ||||||
Percent blast count at diagnosis (in %, n = 47) | ||||||||||||||||||
≤50 | 3 | 8 | 0.588 | 4 | 7 | 0.718 | 0 | 11 | 0.147 | 0 | 11 | 0.065 | 6 | 5 | 0.918 | 0 | 11 | 0.576 |
>50 | 13 | 23 | 11 | 25 | 6 | 30 | 9 | 27 | 19 | 17 | 1 | 35 | ||||||
Subtypes (n = 52) | ||||||||||||||||||
M0 | 1 | 2 | 0.602 | 3 | 0 | 0.634 | 0 | 3 | 0.932 | 0 | 3 | 0.788 | 3 | 0 | 0.053 | 0 | 3 | 0.364 |
M1 | 4 | 8 | 9 | 3 | 1 | 11 | 3 | 9 | 5 | 7 | 0 | 12 | ||||||
M2 | 6 | 6 | 7 | 5 | 2 | 10 | 2 | 10 | 9 | 3 | 0 | 12 | ||||||
M3 | 1 | 2 | 2 | 1 | 0 | 3 | 1 | 2 | 2 | 1 | 0 | 3 | ||||||
M4 | 3 | 9 | 9 | 3 | 1 | 11 | 1 | 11 | 2 | 10 | 0 | 12 | ||||||
M5 | 1 | 6 | 6 | 1 | 1 | 6 | 1 | 6 | 3 | 4 | 1 | 6 | ||||||
M6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | - | - | 0 | 0 | ||||||
M7 | 0 | 3 | 3 | 0 | 0 | 3 | 0 | 3 | 1 | 2 | 0 | 3 | ||||||
Events | ||||||||||||||||||
Relapse (n = 57) | ||||||||||||||||||
Yes | 3 | 12 | 0.202 | 4 | 11 | 0.755 | 0 | 15 | 0.122 | 1 | 14 | 0.197 | 8 | 7 | 0.704 | 0 | 15 | 0.547 |
No | 16 | 26 | 13 | 29 | 6 | 36 | 9 | 33 | 20 | 22 | 1 | 41 | ||||||
Death (n = 57) | ||||||||||||||||||
Yes | 5 | 10 | 1 | 5 | 10 | 0.729 | 5 | 10 | 0.001 | 5 | 10 | 0.061 | 7 | 8 | 0.825 | 1 | 14 | 0.091 |
No | 14 | 28 | 12 | 30 | 1 | 41 | 5 | 37 | 21 | 21 | 0 | 42 | ||||||
Progressive disease (n = 57) | ||||||||||||||||||
Yes | 2 | 4 | 1 | 1 | 5 | 0.456 | 0 | 6 | 0.374 | 0 | 6 | 0.232 | 3 | 3 | 0.964 | 0 | 6 | 0.621 |
No | 17 | 34 | 16 | 35 | 6 | 45 | 10 | 41 | 25 | 26 | 2 | 49 |
METTL3 | p Value | METTL14 | p Value | YTHDF1 | p Value | YTHDF2 | p Value | FTO | p Value | ALKBH5 | p Value | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
+ | − | + | − | + | − | + | − | + | − | + | − | |||||||
AML1-ETO (n = 57) | ||||||||||||||||||
+ | 6 | 10 | 0.677 | 7 | 9 | 0.151 | 1 | 15 | 0.511 | 3 | 13 | 0.881 | 9 | 7 | 0.501 | 0 | 16 | 0.529 |
− | 13 | 28 | 10 | 31 | 5 | 36 | 7 | 34 | 19 | 22 | 1 | 40 | ||||||
CBFB-MYH11 (n = 57) | ||||||||||||||||||
+ | 2 | 3 | 0.741 | 2 | 3 | 0.603 | 1 | 4 | 0.47 | 1 | 4 | 0.88 | 3 | 2 | 0.61 | 0 | 5 | 0.754 |
− | 17 | 35 | 15 | 37 | 5 | 47 | 9 | 43 | 25 | 27 | 1 | 51 | ||||||
RBM15 MKL1 (n = 57) | ||||||||||||||||||
+ | 1 | 0 | 0.154 | 1 | 0 | 0.122 | 0 | 1 | 0.729 | 1 | 0 | 0.029 | 1 | 0 | 0.305 | 0 | 1 | 0.893 |
− | 18 | 38 | 16 | 40 | 6 | 50 | 9 | 47 | 27 | 29 | 1 | 55 | ||||||
NPM1 (n = 57) | ||||||||||||||||||
+ | 1 | 0 | 0.154 | 1 | 0 | 0.122 | 0 | 1 | 0.729 | 1 | 0 | 0.029 | 1 | 0 | 0.305 | 0 | 1 | 0.893 |
− | 18 | 38 | 16 | 40 | 6 | 50 | 9 | 47 | 27 | 29 | 1 | 55 | ||||||
C-KIT (n = 57) | ||||||||||||||||||
+ | 8 | 9 | 0.152 | 9 | 8 | 0.013 | 3 | 14 | 0.253 | 4 | 13 | 0.439 | 9 | 8 | 0.707 | 1 | 16 | 0.122 |
− | 11 | 29 | 8 | 32 | 3 | 37 | 6 | 34 | 19 | 21 | 0 | 40 | ||||||
DEK-CAN (n = 57) | ||||||||||||||||||
+ | 0 | 3 | 0.208 | 0 | 3 | 0.246 | 0 | 3 | 0.542 | 0 | 3 | 0.412 | 1 | 2 | 0.52 | 0 | 3 | 0.812 |
− | 19 | 35 | 17 | 37 | 6 | 48 | 10 | 44 | 27 | 27 | 1 | 53 | ||||||
FLT3-ITD(n = 57) | ||||||||||||||||||
+ | 0 | 10 | 0.014 | 0 | 10 | 0.023 | 0 | 10 | 0.232 | 0 | 10 | 0.108 | 4 | 6 | 0.525 | 0 | 10 | 0.642 |
− | 19 | 28 | 17 | 30 | 6 | 41 | 10 | 37 | 24 | 23 | 1 | 46 | ||||||
PML-RARA (n = 57) | ||||||||||||||||||
+ | 1 | 3 | 0.714 | 1 | 3 | 0.827 | 0 | 4 | 0.477 | 1 | 3 | 0.684 | 3 | 1 | 0.283 | 0 | 4 | 0.782 |
− | 18 | 35 | 16 | 37 | 6 | 47 | 9 | 44 | 25 | 28 | 1 | 52 |
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Kaur, P.; Rajitha, B.; Jain, R.; Sharma, P.; Bhatia, P.; Naseem, S.; Trehan, A.; Singh, M. Altered Expression of m6A-Associated Genes Is Linked with Poor Prognosis in Pediatric Acute Myeloid Leukemia Patients. Biomolecules 2025, 15, 1238. https://doi.org/10.3390/biom15091238
Kaur P, Rajitha B, Jain R, Sharma P, Bhatia P, Naseem S, Trehan A, Singh M. Altered Expression of m6A-Associated Genes Is Linked with Poor Prognosis in Pediatric Acute Myeloid Leukemia Patients. Biomolecules. 2025; 15(9):1238. https://doi.org/10.3390/biom15091238
Chicago/Turabian StyleKaur, Parminder, Bollipogu Rajitha, Richa Jain, Pankaj Sharma, Prateek Bhatia, Shano Naseem, Amita Trehan, and Minu Singh. 2025. "Altered Expression of m6A-Associated Genes Is Linked with Poor Prognosis in Pediatric Acute Myeloid Leukemia Patients" Biomolecules 15, no. 9: 1238. https://doi.org/10.3390/biom15091238
APA StyleKaur, P., Rajitha, B., Jain, R., Sharma, P., Bhatia, P., Naseem, S., Trehan, A., & Singh, M. (2025). Altered Expression of m6A-Associated Genes Is Linked with Poor Prognosis in Pediatric Acute Myeloid Leukemia Patients. Biomolecules, 15(9), 1238. https://doi.org/10.3390/biom15091238