Distinct Mitochondrial DNA Deletion Profiles in Pediatric B- and T-ALL During Diagnosis, Remission, and Relapse
Abstract
1. Introduction
2. Results
2.1. Differential mtDNA Deletion Landscapes in Acute Lymphoblastic Leukemia Subtypes and Control Groups
2.2. Mitochondrial Deletion Profiles Reveal Dynamic Patterns Across Disease Stages, Tumor Types, and Subtypes in Acute Lymphoblastic Leukemia
2.3. Variability and Characteristics of mtDNA Deletions in Pediatric Acute Lymphoblastic Leukemia
2.4. Clusters of Large Mitochondrial DNA Deletions in Pediatric Patients with B-ALL and T-ALL
2.5. Cases of Unusually Large mtDNA Deletion During Remission
2.6. Common and Distinct Repeat Patterns at mtDNA Deletion Breakpoints in B-ALL and T-ALL
2.7. MT-ND5 as the Gene Most Frequently Implicated by mtDNA Deletions in Leukemia
2.8. Multivariate Analysis of Variance (MANOVA) Reveals Significant Effects of Disease, Timepoint, and WHO Subtype on Mitochondrial DNA Deletion Metrics
2.9. Patterns of mtDNA SNVs and Indels in B-ALL and T-ALL
3. Discussion
3.1. Mitochondrial DNA Deletion Profiles in B-ALL and T-ALL
3.2. Possible Mechanisms Underlying Mtdna Deletions
3.3. Implications of Large Mtdna Deletions During Remission
3.4. Mitochondrial DNA Deletion Patterns as Biomarkers of Disease Progression
4. Materials and Methods
4.1. Patient Samples and Study Design
4.2. DNA Extraction
4.3. Mitochondrial DNA Sequencing
4.4. Bioinformatic Analysis
4.4.1. Mitochondrial DNA Deletions
4.4.2. Mitochondrial DNA SNVs and Indels
4.4.3. Statistical Analysis
4.4.4. Repeat Pattern Analysis
4.4.5. Comparative Analysis of Deletion Profiles
4.4.6. Distance-Based Clustering and Ordination
4.5. Code Availability
4.6. Use of Large Language Model for Proof-Editing
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
B-ALL | B-cell acute lymphoblastic leukemia |
T-ALL | T-cell acute lymphoblastic leukemia |
KSS | Kearns–Sayre syndrome |
PEO | progressive external ophthalmoplegia |
UCI/SBB | University of California Irvine/Strategic Behavioral Sciences |
CHLA | Children’s Hospital Los Angeles |
LR-PCR | long-range PCR |
PERMANOVA | permutational multivariate analysis of variance |
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MapSplice Breakpoints | Gene Location | Perfect Repeat | MapSplice Break | Imperfect_5p | Imperfect_3p | Frequency | Mean Deletion Percent | Perfect Length | GC Content |
---|---|---|---|---|---|---|---|---|---|
14054-14377 | (MT-ND5-MT-ND6) | CACAGCACCAA | GC | AAAACAATTTCACAGCACCAAATCTCCACCT | CTCTTTCACCCACAGCACCAATCCTACCTCC | 35 | 0.16 | 11 | 54.5 |
8471-13449 | (MT-ATP8-MT-ND5) | ACCTCCCTCACCA | CC | ACTACCACCTACCTCCCTCACCAAAGCCCATAA | TCTCACTTCAACCTCCCTCACCATTGGCAGCCT | 34 | 0.15 | 13 | 61.5 |
6545-13846 | (MT-CO1-MT-ND5) | ACCTCAAC | TC | ACAGACCGCAACCTCAACACCACCTTCT | ACAGCCCTAGACCTCAACTACCTAACCA | 30 | 0.15 | 8 | 50.0 |
6335-13999 | (MT-CO1-MT-ND5) | TAGACCTAACC | CC | GGAGCCTCCGTAGACCTAACCATCTTCTCCT | CTACTCCTCCTAGACCTAACCTGACTAGAAA | 29 | 0.11 | 11 | 45.5 |
14066-14413 | (MT-ND5-MT-ND6) | ACCTCAACCC | CA | CTCCATCATCACCTCAACCCAAAAAGGCAT | ACTCACCAAGACCTCAACCCCTGACCCCCA | 27 | 0.10 | 10 | 60.0 |
5368-15335 | (MT-ND2-MT-CYB) | ACTCCACCTC | CA | CGCCTAATCTACTCCACCTCAATCACACTA | CCCTAGCAACACTCCACCTCCTATTCTTGC | 22 | 0.10 | 10 | 60.0 |
511-13926 | (D-Loop2-MT-ND5) | CACACACCGC | CA | ACCCAGCACACACACACCGCTGCTAACCCC | ACCCTAGCATCACACACCGCACAATCCCCT | 21 | 0.26 | 10 | 70.0 |
2224-13792 | (MT-RNR2-MT-ND5) | CTACCTAAAA | CT | TCAACACCCACTACCTAAAAAATCCCAAAC | CAATCCCCCTCTACCTAAAACTCACAGCCC | 21 | 0.10 | 10 | 30.0 |
1105-13846 | (MT-RNR1-MT-ND5) | ACCTCAAC | TC | TTAGCCCTAAACCTCAACAGTTAAATCA | ACAGCCCTAGACCTCAACTACCTAACCA | 21 | 0.10 | 8 | 50.0 |
Category | Subcategory | Patient Count (Sample Count) |
---|---|---|
Age Group | unknown | 6 |
0–4 Years | 30 | |
5–10 Years | 42 | |
11–15 Years | 23 | |
16–20 Years | 16 | |
Gender * | unknown | 6 |
Female | 45 | |
Male | 66 | |
Disease | B_ALL | 93 (105) |
Control (Non-Leuk) | 12 (12) | |
T_ALL | 28 (31) | |
Timepoint | Control | 12 (12) |
Diagnosis | 111 (111) | |
Relapse | 20 (23) | |
Remission | 6 (8) | |
Totals | 129 (148) |
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Hakimjavadi, H.; Eom, E.; Christodoulou, E.; Hjelm, B.E.; Omidsalar, A.A.; Ostrow, D.; Biegel, J.A.; Gai, X. Distinct Mitochondrial DNA Deletion Profiles in Pediatric B- and T-ALL During Diagnosis, Remission, and Relapse. Int. J. Mol. Sci. 2025, 26, 7117. https://doi.org/10.3390/ijms26157117
Hakimjavadi H, Eom E, Christodoulou E, Hjelm BE, Omidsalar AA, Ostrow D, Biegel JA, Gai X. Distinct Mitochondrial DNA Deletion Profiles in Pediatric B- and T-ALL During Diagnosis, Remission, and Relapse. International Journal of Molecular Sciences. 2025; 26(15):7117. https://doi.org/10.3390/ijms26157117
Chicago/Turabian StyleHakimjavadi, Hesamedin, Elizabeth Eom, Eirini Christodoulou, Brooke E. Hjelm, Audrey A. Omidsalar, Dejerianne Ostrow, Jaclyn A. Biegel, and Xiaowu Gai. 2025. "Distinct Mitochondrial DNA Deletion Profiles in Pediatric B- and T-ALL During Diagnosis, Remission, and Relapse" International Journal of Molecular Sciences 26, no. 15: 7117. https://doi.org/10.3390/ijms26157117
APA StyleHakimjavadi, H., Eom, E., Christodoulou, E., Hjelm, B. E., Omidsalar, A. A., Ostrow, D., Biegel, J. A., & Gai, X. (2025). Distinct Mitochondrial DNA Deletion Profiles in Pediatric B- and T-ALL During Diagnosis, Remission, and Relapse. International Journal of Molecular Sciences, 26(15), 7117. https://doi.org/10.3390/ijms26157117