PPM1D Mutation as a Distinct Feature of Myeloid Neoplasms in B-Cell Non-Hodgkin Lymphoma Patients: A Retrospective Analysis
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient
2.2. Study Design
2.3. Samples Collection and Processing for NGS Analysis
2.4. Next-Generation Sequencing Analysis
2.5. Statistical Analysis
3. Results
3.1. Characteristics of Patients with B-Cell Non-Hodgkin Lymphoma
3.2. Genetic Features of Myeloid Neoplasms After B-Cell Non-Hodgkin Lymphoma
3.3. Comparison of Clinicopathologic and Genetic Features of Myeloid Neoplasms After B-Cell Non-Hodgkin Lymphoma and Solid Cancer
3.4. Survival Analysis
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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Characteristics | BNHL (n = 16) |
---|---|
Age of diagnosis of BNHL, years | 56.7 ± 11.5 |
Male gender, n (%) | 10 (63%) |
Stage * | |
I | 1 (6%) |
II | 2 (13%) |
III | 3 (19%) |
IV | 10 (63%) |
Pathologic diagnosis | |
DLBL | 7 (44%) |
FL | 4 (25%) |
MZBL CLL MCL | 2 (13%) 1 (6%) 2 (13%) |
Cytotoxic therapy exposure | 16 (100%) |
Chemotherapy only | 2 (13%) |
Chemotherapy + RIT | 1 (6%) |
Chemotherapy + RIT + RT | 1 (6%) |
Immunochemotherapy (rituximab) combination | 12 (75%) |
Immunochemotherapy | 2 (13%) |
Immunochemotherapy + RIT | 7 (44%) |
Immunochemotherapy + RIT + RT | 3 (19%) |
Treatment response (IWC + PET criteria) | |
CR | 10 (63%) |
PR | 2 (13%) |
SD | 2 (13%) |
PD | 1 (6%) |
NA | 1 (6%) |
Relapse | |
NA | 1 (8%) |
CR or PR | 3 (25%) |
Relapse | 8 (67%) |
Characteristics | MN-BNHL (n = 16) | MN-SC † (n = 21) | p-Value |
---|---|---|---|
Age, years at diagnosis of MN | 66.5 (57.5, 72) | 63 (57, 67) | 0.3735 |
Exposure to cytotoxic therapies | |||
Chemotherapy | 16 (100%) | 19 (90%) | 0.4955 |
Rituximab | 12 (75%) | 0 (0%) | <0.001 |
Radiotherapy | 4 (25%) | 12 (57%) | 0.1052 |
RIT/RAI | 12 (75%) | 1 (5%) | <0.001 |
Interval period, year (range) | 7.0 ± 4.0 (2.4 to 17.3) | 11.7 ± 8.3 (1.3 to 28) | 0.0305 |
Survival state | |||
Death | 14 (88%) | 10 (48%) | 0.03 |
Survival period after MN, month (range) | 11 (4.8–19.8) | 6 (2–10) | 0.1574 |
Follow-up period, year (range) | 9.0 ± 4.3 (2.8–18.6) | 12.4 ± 8.4 (1.3–28.4) | 0.1183 |
BM study | |||
Blast count (%) | 6.9 (4.5, 16.9) | 14.6 (6, 46.6) | 0.2696 |
Dysplasia (>10%) | |||
Dyserythropoiesis | 10 (63%) | 8 (42%) | 0.388 |
Dysgranulopoiesis | 2 (13%) | 4 (21%) | 0.6657 |
Dysmegakaryopoiesis | 6 (43%) | 15 (83%) | 0.0265 |
BM Fibrosis (≥MF − 1) | 0 (0%) | 10 (59%) | <0.001 |
Chromosomal aberrations | |||
Complex karyotype | 11 (69%) | 13 (62%) | 0.9326 |
–7/del7q | 10 (63%) | 8 (38%) | 0.2545 |
–5/del5q | 4 (25%) | 9 (45%) | 0.3722 |
i (17q), –17/add(17p) or del(17p) | 4 (25%) | 1 (5%) | 0.1444 |
–20/del20q | 1 (6%) | 3 (15%) | 0.6129 |
Somatic mutations associated with myeloid neoplasms * (3 dominant tier-1-mutated genes) | |||
PPM1D | 8 (73%) | 2 (10%) | <0.001 |
TP53 | 4 (36%) | 13 (62%) | 0.2818 |
DNMT3A | 5 (45%) | 2 (10%) | 0.0318 |
Treatment/Gene Mutation | Relative Risk (95% CI) | |||
---|---|---|---|---|
Chemotherapy | Rituximab (Immunochemotherapy) | RIT/RAI | Radiotherapy | |
PPM1Dm (+) | 1.07 (0.88, 1.30) | 3.67 (1.08, 12.43) | 3.3 (1.19, 9.16) | 0.51 (0.19, 1.39) |
TP53m (+) | 1.15 (0.92, 1.44) | 0.88 (0.26, 2.92) | 0.59 (0.20, 1.69) | 1.13 (0.56, 2.29) |
DNMT3Am (+) | 1.03 (0.83, 1.29) | 2.14 (0.67, 6.83) | 3.57 (1.43, 8.90) | 0.51 (0.15, 1.73) |
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Kim, H.; Lee, J.K.; Hong, Y.J.; Kang, H.J.; Byun, B.H.; Lee, S.-S. PPM1D Mutation as a Distinct Feature of Myeloid Neoplasms in B-Cell Non-Hodgkin Lymphoma Patients: A Retrospective Analysis. Cancers 2025, 17, 1185. https://doi.org/10.3390/cancers17071185
Kim H, Lee JK, Hong YJ, Kang HJ, Byun BH, Lee S-S. PPM1D Mutation as a Distinct Feature of Myeloid Neoplasms in B-Cell Non-Hodgkin Lymphoma Patients: A Retrospective Analysis. Cancers. 2025; 17(7):1185. https://doi.org/10.3390/cancers17071185
Chicago/Turabian StyleKim, Heyjin, Jin Kyung Lee, Young Jun Hong, Hye Jin Kang, Byung Hyun Byun, and Seung-Sook Lee. 2025. "PPM1D Mutation as a Distinct Feature of Myeloid Neoplasms in B-Cell Non-Hodgkin Lymphoma Patients: A Retrospective Analysis" Cancers 17, no. 7: 1185. https://doi.org/10.3390/cancers17071185
APA StyleKim, H., Lee, J. K., Hong, Y. J., Kang, H. J., Byun, B. H., & Lee, S.-S. (2025). PPM1D Mutation as a Distinct Feature of Myeloid Neoplasms in B-Cell Non-Hodgkin Lymphoma Patients: A Retrospective Analysis. Cancers, 17(7), 1185. https://doi.org/10.3390/cancers17071185