Loss of Heterozygosity in Pediatric Acute Lymphoblastic Leukemia and Its Prognostic Impact: A Retrospective Study
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants and Study Design
2.2. Microarray Analysis
2.3. Experimental Design
2.4. Criteria of Experimental Group
2.5. Statistical Analysis
2.5.1. Significance Level and Selection of Analytical Methods
2.5.2. Patient Clustering
2.5.3. Role and Interpretation of Clusters and Dimensions
2.5.4. Analysis Objective and Input Variables
2.5.5. Clustering Results: B-ALL and T-ALL Cohorts
3. Results
3.1. Genetics Characteristics of B-ALL with LOH
3.2. Clinical Characteristics of B-ALL with LOH
3.3. Genetic Characteristics of T-ALL with LOH
3.4. Clinical Characteristics of T-ALL Group
3.5. Chromothripsis
4. Discussion
4.1. B-ALL
4.1.1. LOH 9/9p and Deletion of CDKN2A/2B
LOH and Biallelic Deletion of CDKN2A
Role in Clonal Evolution of LOH on the Entire Chromosome 9
LOH in Other Chromosomal Regions: 6p and 12p/q
The Role of LOH 9p in the Pathogenesis of ALL
4.1.2. Clinical Implications of LOH 9/9p
Profiles of Patients—Cluster 1
Profiles of Patients—Cluster 2
Profiles of Patients—Cluster 3
4.2. T-ALL
4.2.1. Profiles of Patients—Cluster 1
4.2.2. Profiles of Patients—Cluster 2
4.2.3. Profiles of Patients—Cluster 3
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ALL | acute lymphoblastic leukemia |
B-ALL | B-cell acute lymphoblastic leukemia |
T-ALL | T-cell acute lymphoblastic leukemia |
LOH | loss of heterozygosity |
CNL-LOH | loss of heterozygosity with copy number losses |
CNN-LOH | copy number neutral loss of heterozygosity |
DNA | deoxyribonucleic acid |
FMC MRD | flow cytometry-minimal residual disease |
MRD/PCR | minimal residual disease detected by polymerase chain reaction |
SNP | single-nucleotide polymorphism |
CNV | copy number variant |
CNAs | copy numbers of altered regions |
ChAS | Chromosome Analysis Suite |
CN | copy number |
kbp | kilobase pair |
Mbp | megabase pair |
BAF | biallelic frequency |
p | short arm of a chromosome |
q | long arm of a chromosome |
MRD | minimal residual disease |
WBC | white blood cells |
NGS | next-generation sequencing |
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Characteristic | B-ALL (N = 120) | T-ALL (N = 58) |
---|---|---|
n (%) | n (%) | |
Age, years | 5.39 (3.38, 9.23) a | 10.33 (4.90, 13.94) a |
Gender: | ||
female | 59 (49.17%) | 24 (41.38%) |
male | 61 (50.83%) | 34 (58.62%) |
WBC [×103/μL] | 7.04 (3.69, 25.00) a | 117.86 (43.93, 247.06) a |
BM, % | 91.00 (84.50, 95.38) a | 90.00 (80.00, 94.95) a |
Response to prednisone: | ||
good | 90 (75.00%) | 36 (62.07%) |
poor | 30 (25.00%) | 22 (37.93%) |
MRD FMC 15 day: | ||
<0.1% | 40 (33.33%) | 11 (18.97%) |
0.1–10% | 69 (57.50%) | 21 (36.21%) |
≥10% | 11 (9.17%) | 26 (44.83%) |
MRD/PCR 33 day: | ||
negative | 48 (40.00%) | 9 (15.52%) |
positive | 72 (60.00%) | 37 (63.79%) |
other (no marker) | 12 (20.69%) |
LOH 9/9p | N | n (%) |
---|---|---|
No evidence of LOH | 63 | 52.5% |
Patients with 9p LOH extending to 9p13 | 6 | 5% |
LOH 9 | 33 | 27.5% |
LOH 9p | 3 | 2.5% |
LOH 9q | 5 | 4.2% |
Patients with interrupted 9p LOH | 10 | 8.3% |
CDKN2A | N | n (%) |
del monoallelic | 24 | 20% |
del biallelic | 19 | 15.8% |
duplication | 14 | 11.7% |
LOH | 24 | 20% |
No alterations | 39 | 32.5% |
LOH 9/9p | N | n (%) |
---|---|---|
No evidence of LOH | 14 | 24% |
Patients with 9p LOH extending to 9p13 | 6 | 10% |
LOH 9 | 0 | 0% |
LOH 9p | 15 | 26% |
Patients with interrupted 9p LOH | 23 | 40% |
CDKN2A | N | n (%) |
del monoallelic | 12 | 21% |
del biallelic | 35 | 60% |
LOH | 3 | 5% |
No alterations | 8 | 14% |
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Styka, B.; Ręka, G.; Ozygała, A.; Janiszewska, M.; Stelmach, M.; Skowera, P.; Urbańska, Z.; Lejman, M. Loss of Heterozygosity in Pediatric Acute Lymphoblastic Leukemia and Its Prognostic Impact: A Retrospective Study. Cancers 2025, 17, 2500. https://doi.org/10.3390/cancers17152500
Styka B, Ręka G, Ozygała A, Janiszewska M, Stelmach M, Skowera P, Urbańska Z, Lejman M. Loss of Heterozygosity in Pediatric Acute Lymphoblastic Leukemia and Its Prognostic Impact: A Retrospective Study. Cancers. 2025; 17(15):2500. https://doi.org/10.3390/cancers17152500
Chicago/Turabian StyleStyka, Borys, Gabriela Ręka, Aleksandra Ozygała, Mariola Janiszewska, Magdalena Stelmach, Paulina Skowera, Zuzanna Urbańska, and Monika Lejman. 2025. "Loss of Heterozygosity in Pediatric Acute Lymphoblastic Leukemia and Its Prognostic Impact: A Retrospective Study" Cancers 17, no. 15: 2500. https://doi.org/10.3390/cancers17152500
APA StyleStyka, B., Ręka, G., Ozygała, A., Janiszewska, M., Stelmach, M., Skowera, P., Urbańska, Z., & Lejman, M. (2025). Loss of Heterozygosity in Pediatric Acute Lymphoblastic Leukemia and Its Prognostic Impact: A Retrospective Study. Cancers, 17(15), 2500. https://doi.org/10.3390/cancers17152500