*Result*: Clinical Impact of MTAP Rearrangement in Pediatric Acute Lymphoblastic Leukemia: Insights From Whole Transcriptome Analysis.
Title:
Clinical Impact of MTAP Rearrangement in Pediatric Acute Lymphoblastic Leukemia: Insights From Whole Transcriptome Analysis.
Authors:
Zhang S; Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.; Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China., Wu Z; Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Liu Y; Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Li B; Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Song Y; Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Source:
Pediatric blood & cancer [Pediatr Blood Cancer] 2026 Feb; Vol. 73 (2), pp. e70012. Date of Electronic Publication: 2025 Nov 19.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: John Wiley Country of Publication: United States NLM ID: 101186624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-5017 (Electronic) Linking ISSN: 15455009 NLM ISO Abbreviation: Pediatr Blood Cancer Subsets: MEDLINE
Imprint Name(s):
Original Publication: Hoboken, N.J. : John Wiley, c 2004-
MeSH Terms:
Gene Rearrangement* , Precursor Cell Lymphoblastic Leukemia-Lymphoma*/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma*/pathology , Gene Expression Profiling* , Biomarkers, Tumor*/genetics , Transcriptome*, Humans ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Prognosis ; Infant ; Adolescent ; Follow-Up Studies ; Survival Rate
References:
F. Malard and M. Mohty, “Acute Lymphoblastic Leukaemia,” Lancet 395, no. 10230 (2020): 1146–1162.
C. H. Pui, D. Pei, S. C. Raimondi, et al., “Clinical Impact of Minimal Residual Disease in Children With Different Subtypes of Acute Lymphoblastic Leukemia Treated With Response‐Adapted Therapy,” Leukemia 31, no. 2 (2017): 333–339.
T. H. Tran and S. P. Hunger, “The Genomic Landscape of Pediatric Acute Lymphoblastic Leukemia and Precision Medicine Opportunities,” Seminars in Cancer Biology 84 (2022): 144–152.
M. Simonin, L. Vasseur, E. Lengliné, et al., “NGS‐based Stratification Refines the Risk Stratification in T‐ALL and Identifies a Very‐high‐risk Subgroup of Patients,” Blood 144, no. 15 (2024): 1570–1580.
A. Quintás‐Cardama and J. Cortes, “Molecular Biology of Bcr‐abl1‐Positive Chronic Myeloid Leukemia,” Blood 113, no. 8 (2009): 1619–1630.
T. P. Hughes, G. Saglio, A. Quintás‐Cardama, et al., “BCR‐ABL1 Mutation Development During First‐line Treatment With Dasatinib or Imatinib for Chronic Myeloid Leukemia in Chronic Phase,” Leukemia 29, no. 9 (2015): 1832–1838.
C. Grant and M. Nagasaka, “Neoadjuvant EGFR‐TKI Therapy in Non‐Small Cell Lung Cancer,” Cancer Treatment Reviews 126 (2024): 102724.
P. Ballard, J. W. Yates, Z. Yang, et al., “Preclinical Comparison of Osimertinib With Other EGFR‐TKIs in EGFR‐Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity,” Clinical Cancer Research 22, no. 20 (2016): 5130–5140.
R. Rosenquist, E. Bernard, T. Erkers, et al., “Novel Precision Medicine Approaches and Treatment Strategies in Hematological Malignancies,” Journal of Internal Medicine 294, no. 4 (2023): 413–436.
K. Davis, T. Sheikh, and N. Aggarwal, “Emerging Molecular Subtypes and Therapies in Acute Lymphoblastic Leukemia,” Seminars in Diagnostic Pathology 40, no. 3 (2023): 202–215.
H. Lilljebjörn, R. Henningsson, A. Hyrenius‐Wittsten, et al., “Identification of ETV6‐RUNX1‐Like and DUX4‐Rearranged Subtypes in Paediatric B‐Cell Precursor Acute Lymphoblastic Leukaemia,” Nature Communications 7 (2016): 11790.
T. C. Chang, W. Chen, C. Qu, et al., “Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia,” Journal of Clinical Oncology 42, no. 29 (2024): 3491–3503.
S. Jeha, J. Choi, K. G. Roberts, et al., “Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease‐Directed Therapy,” Blood Cancer Discovery 2, no. 4 (2021): 326–337.
O. I. Olopade, H. M. Pomykala, F. Hagos, et al., “Construction of a 2.8‐Megabase Yeast Artificial Chromosome Contig and Cloning of the Human Methylthioadenosine Phosphorylase Gene From the Tumor Suppressor Region on 9p21,” Proceedings of the National Academy of Sciences of the United States of America 92, no. 14 (1995): 6489–6493.
T. Nobori, K. Takabayashi, P. Tran, et al., “Genomic Cloning of Methylthioadenosine Phosphorylase: A Purine Metabolic Enzyme Deficient in Multiple Different Cancers,” Proceedings of the National Academy of Sciences of the United States of America 93, no. 12 (1996): 6203–6208.
S. F. de Oliveira, M. Ganzinelli, R. Chilà, et al., “Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines,” PLOS One 11, no. 1 (2016): e0145647.
Z. Lin, Y. Lei, M. Wen, Q. He, D. Tian, and H. Xie, “MTAP‐ANRIL Gene Fusion Promotes Melanoma Epithelial‐Mesenchymal Transition‐Like Process by Activating the JNK and p38 Signaling Pathways,” Scientific Reports 13, no. 1 (2023): 9073.
C. P. K. Patro, N. Biswas, S. C. Pingle, et al., “MTAP Loss: A Possible Therapeutic Approach for Glioblastoma,” Journal of Translational Medicine 20, no. 1 (2022): 620.
Y. Zhong, K. Lu, S. Zhu, W. Li, and S. Sun, “Characterization of Methylthioadenosin Phosphorylase (MTAP) Expression in Colorectal Cancer,” Artificial Cells, Nanomedicine, and Biotechnology 46, no. 8 (2018): 2082–2087.
L. D. Engstrom, R. Aranda, L. Waters, et al., “MRTX1719 Is an MTA‐Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients With MTAP‐Deleted Cancer,” Cancer Discovery 13, no. 11 (2023): 2412–2431.
T. Efferth, H. Miyachi, H. G. Drexler, and E. Gebhart, “Methylthioadenosine Phosphorylase as Target for Chemoselective Treatment of T‐Cell Acute Lymphoblastic Leukemic Cells,” Blood Cells, Molecules & Diseases 28, no. 1 (2002): 47–56.
J. R. Bertino, W. R. Waud, W. B. Parker, and M. Lubin, “Targeting Tumors That Lack Methylthioadenosine Phosphorylase (MTAP) Activity: Current Strategies,” Cancer Biology & Therapy 11, no. 7 (2011): 627–632.
P. Carrasco Salas, L. Fernández, M. Vela, et al., “The Role of CDKN2A/B Deletions in Pediatric Acute Lymphoblastic Leukemia,” Pediatric Hematology and Oncology 33, no. 7–8 (2016): 415–422.
A. Batova, M. B. Diccianni, T. Nobori, et al., “Frequent Deletion in the Methylthioadenosine Phosphorylase Gene in T‐Cell Acute Lymphoblastic Leukemia: Strategies for Enzyme‐Targeted Therapy,” Blood 88, no. 8 (1996): 3083–3090.
N. Fan, Y. Zhang, and S. Zou, “Methylthioadenosine Phosphorylase Deficiency in Tumors: A Compelling Therapeutic Target,” Frontiers in Cell and Developmental Biology 11 (2023): 1173356.
Q. Hu, Y. Qin, S. Ji, et al., “MTAP Deficiency‐Induced Metabolic Reprogramming Creates a Vulnerability to Cotargeting De Novo Purine Synthesis and Glycolysis in Pancreatic Cancer,” Cancer Research 81, no. 19 (2021): 4964–4980.
K. J. Mavrakis, E. R. McDonald 3rd, M. R. Schlabach, et al., “Disordered Methionine Metabolism in MTAP/CDKN2A‐Deleted Cancers Leads to Dependence on PRMT5,” Science 351, no. 6278 (2016): 1208–1213.
W. H. Chang, S. W. Hsu, J. Zhang, et al., “MTAP Deficiency Contributes to Immune Landscape Remodelling and Tumour Evasion,” Immunology 168, no. 2 (2023): 331–345.
D. Gjuka, E. Adib, K. Garrison, et al., “Enzyme‐mediated Depletion of Methylthioadenosine Restores T Cell Function in MTAP‐Deficient Tumors and Reverses Immunotherapy Resistance,” Cancer Cell 41, no. 10 (2023): 1774–1787.e9.
W. Xu, A. Anwaier, W. Liu, et al., “Genomic Alteration of MTAP/CDKN2A Predicts Sarcomatoid Differentiation and Poor Prognosis and Modulates Response to Immune Checkpoint Blockade in Renal Cell Carcinoma,” Frontiers in Immunology 13 (2022): 953721.
O. Alhalabi, Y. Zhu, A. Hamza, et al., “Integrative Clinical and Genomic Characterization of MTAP‐Deficient Metastatic Urothelial Cancer,” European Urology Oncology 6, no. 2 (2023): 228–232.
C. F. Gaspar, N. Y. Ngoi, T. Tang, et al., “Abstract 963: Clinical Impact of MTAP Status in Advanced Cholangiocarcinoma: Genomic Profile and Response to Treatment,” Cancer Research 83, no. 7_Supplement (2023): 963.
D. Owen, R. Ben‐Shachar, J. Feliciano, et al., “Actionable Structural Variant Detection via RNA‐NGS and DNA‐NGS in Patients With Advanced Non‐Small Cell Lung Cancer,” JAMA Network Open 7, no. 11 (2024): e2442970.
J. Buckley, R. J. Schmidt, D. Ostrow, et al., “An Exome Capture‐Based RNA‐Sequencing Assay for Genome‐Wide Identification and Prioritization of Clinically Important Fusions in Pediatric Tumors,” Journal of Molecular Diagnostics 26, no. 2 (2024): 127–139.
K. Marjon, M. J. Cameron, P. Quang, et al., “MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis,” Cell Reports 15, no. 3 (2016): 574–587.
M. M. Fischer, K. Gerrick, B. Belmontes, et al., “Abstract 1644: Dual Inhibition of MAT2A and PRMT5 Delivers Synergistic Anti‐Tumor Responses in Preclinical Models of MTAP‐Deleted Cancer,” Cancer Research 83, no. 7_Supplement (2023): 1644.
B. Subramaniam, B. Kritzer, E. Putnam, et al., “HGG‐02. Metabolic Targeting of High‐Grade Gliomas With MTAP Loss,” Neuro‐Oncology 25, no. Supplement_1 (2023): i38.
G. Gao, L. Zhang, O. D. Villarreal, et al., “PRMT1 Loss Sensitizes Cells to PRMT5 Inhibition,” Nucleic Acids Research 47, no. 10 (2019): 5038–5048.
G. T. Bedard, N. Gilaj, K. Peregrina, et al., “Combined Inhibition of MTAP and MAT2a Mimics Synthetic Lethality in Tumor Models via PRMT5 Inhibition,” Journal of Biological Chemistry 300, no. 1 (2024): 105492.
C. L. Neilan, M. M. Fischer, D. Garbett, et al., “Abstract B027: The MAT2A Inhibitor IDE397: A Novel Combination Backbone for Urothelial Cancer Subjects With MTAP Deficiency,” Clinical Cancer Research 30, no. 10_Supplement (2024): B027–B.
P. A. Shah, A. K. Saw, W. Padron, et al., “Abstract 4536: MTAP Loss Alters the Epigenetic Landscape and Demonstrates Superior Therapeutic Sensitivity to Concomitant PRMT5 and PARP Inhibition in Cholangiocarcinoma,” Cancer Research 84, no. 6_Supplement (2024): 4536.
C. H. Pui, D. Pei, S. C. Raimondi, et al., “Clinical Impact of Minimal Residual Disease in Children With Different Subtypes of Acute Lymphoblastic Leukemia Treated With Response‐Adapted Therapy,” Leukemia 31, no. 2 (2017): 333–339.
T. H. Tran and S. P. Hunger, “The Genomic Landscape of Pediatric Acute Lymphoblastic Leukemia and Precision Medicine Opportunities,” Seminars in Cancer Biology 84 (2022): 144–152.
M. Simonin, L. Vasseur, E. Lengliné, et al., “NGS‐based Stratification Refines the Risk Stratification in T‐ALL and Identifies a Very‐high‐risk Subgroup of Patients,” Blood 144, no. 15 (2024): 1570–1580.
A. Quintás‐Cardama and J. Cortes, “Molecular Biology of Bcr‐abl1‐Positive Chronic Myeloid Leukemia,” Blood 113, no. 8 (2009): 1619–1630.
T. P. Hughes, G. Saglio, A. Quintás‐Cardama, et al., “BCR‐ABL1 Mutation Development During First‐line Treatment With Dasatinib or Imatinib for Chronic Myeloid Leukemia in Chronic Phase,” Leukemia 29, no. 9 (2015): 1832–1838.
C. Grant and M. Nagasaka, “Neoadjuvant EGFR‐TKI Therapy in Non‐Small Cell Lung Cancer,” Cancer Treatment Reviews 126 (2024): 102724.
P. Ballard, J. W. Yates, Z. Yang, et al., “Preclinical Comparison of Osimertinib With Other EGFR‐TKIs in EGFR‐Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity,” Clinical Cancer Research 22, no. 20 (2016): 5130–5140.
R. Rosenquist, E. Bernard, T. Erkers, et al., “Novel Precision Medicine Approaches and Treatment Strategies in Hematological Malignancies,” Journal of Internal Medicine 294, no. 4 (2023): 413–436.
K. Davis, T. Sheikh, and N. Aggarwal, “Emerging Molecular Subtypes and Therapies in Acute Lymphoblastic Leukemia,” Seminars in Diagnostic Pathology 40, no. 3 (2023): 202–215.
H. Lilljebjörn, R. Henningsson, A. Hyrenius‐Wittsten, et al., “Identification of ETV6‐RUNX1‐Like and DUX4‐Rearranged Subtypes in Paediatric B‐Cell Precursor Acute Lymphoblastic Leukaemia,” Nature Communications 7 (2016): 11790.
T. C. Chang, W. Chen, C. Qu, et al., “Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia,” Journal of Clinical Oncology 42, no. 29 (2024): 3491–3503.
S. Jeha, J. Choi, K. G. Roberts, et al., “Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease‐Directed Therapy,” Blood Cancer Discovery 2, no. 4 (2021): 326–337.
O. I. Olopade, H. M. Pomykala, F. Hagos, et al., “Construction of a 2.8‐Megabase Yeast Artificial Chromosome Contig and Cloning of the Human Methylthioadenosine Phosphorylase Gene From the Tumor Suppressor Region on 9p21,” Proceedings of the National Academy of Sciences of the United States of America 92, no. 14 (1995): 6489–6493.
T. Nobori, K. Takabayashi, P. Tran, et al., “Genomic Cloning of Methylthioadenosine Phosphorylase: A Purine Metabolic Enzyme Deficient in Multiple Different Cancers,” Proceedings of the National Academy of Sciences of the United States of America 93, no. 12 (1996): 6203–6208.
S. F. de Oliveira, M. Ganzinelli, R. Chilà, et al., “Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines,” PLOS One 11, no. 1 (2016): e0145647.
Z. Lin, Y. Lei, M. Wen, Q. He, D. Tian, and H. Xie, “MTAP‐ANRIL Gene Fusion Promotes Melanoma Epithelial‐Mesenchymal Transition‐Like Process by Activating the JNK and p38 Signaling Pathways,” Scientific Reports 13, no. 1 (2023): 9073.
C. P. K. Patro, N. Biswas, S. C. Pingle, et al., “MTAP Loss: A Possible Therapeutic Approach for Glioblastoma,” Journal of Translational Medicine 20, no. 1 (2022): 620.
Y. Zhong, K. Lu, S. Zhu, W. Li, and S. Sun, “Characterization of Methylthioadenosin Phosphorylase (MTAP) Expression in Colorectal Cancer,” Artificial Cells, Nanomedicine, and Biotechnology 46, no. 8 (2018): 2082–2087.
L. D. Engstrom, R. Aranda, L. Waters, et al., “MRTX1719 Is an MTA‐Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients With MTAP‐Deleted Cancer,” Cancer Discovery 13, no. 11 (2023): 2412–2431.
T. Efferth, H. Miyachi, H. G. Drexler, and E. Gebhart, “Methylthioadenosine Phosphorylase as Target for Chemoselective Treatment of T‐Cell Acute Lymphoblastic Leukemic Cells,” Blood Cells, Molecules & Diseases 28, no. 1 (2002): 47–56.
J. R. Bertino, W. R. Waud, W. B. Parker, and M. Lubin, “Targeting Tumors That Lack Methylthioadenosine Phosphorylase (MTAP) Activity: Current Strategies,” Cancer Biology & Therapy 11, no. 7 (2011): 627–632.
P. Carrasco Salas, L. Fernández, M. Vela, et al., “The Role of CDKN2A/B Deletions in Pediatric Acute Lymphoblastic Leukemia,” Pediatric Hematology and Oncology 33, no. 7–8 (2016): 415–422.
A. Batova, M. B. Diccianni, T. Nobori, et al., “Frequent Deletion in the Methylthioadenosine Phosphorylase Gene in T‐Cell Acute Lymphoblastic Leukemia: Strategies for Enzyme‐Targeted Therapy,” Blood 88, no. 8 (1996): 3083–3090.
N. Fan, Y. Zhang, and S. Zou, “Methylthioadenosine Phosphorylase Deficiency in Tumors: A Compelling Therapeutic Target,” Frontiers in Cell and Developmental Biology 11 (2023): 1173356.
Q. Hu, Y. Qin, S. Ji, et al., “MTAP Deficiency‐Induced Metabolic Reprogramming Creates a Vulnerability to Cotargeting De Novo Purine Synthesis and Glycolysis in Pancreatic Cancer,” Cancer Research 81, no. 19 (2021): 4964–4980.
K. J. Mavrakis, E. R. McDonald 3rd, M. R. Schlabach, et al., “Disordered Methionine Metabolism in MTAP/CDKN2A‐Deleted Cancers Leads to Dependence on PRMT5,” Science 351, no. 6278 (2016): 1208–1213.
W. H. Chang, S. W. Hsu, J. Zhang, et al., “MTAP Deficiency Contributes to Immune Landscape Remodelling and Tumour Evasion,” Immunology 168, no. 2 (2023): 331–345.
D. Gjuka, E. Adib, K. Garrison, et al., “Enzyme‐mediated Depletion of Methylthioadenosine Restores T Cell Function in MTAP‐Deficient Tumors and Reverses Immunotherapy Resistance,” Cancer Cell 41, no. 10 (2023): 1774–1787.e9.
W. Xu, A. Anwaier, W. Liu, et al., “Genomic Alteration of MTAP/CDKN2A Predicts Sarcomatoid Differentiation and Poor Prognosis and Modulates Response to Immune Checkpoint Blockade in Renal Cell Carcinoma,” Frontiers in Immunology 13 (2022): 953721.
O. Alhalabi, Y. Zhu, A. Hamza, et al., “Integrative Clinical and Genomic Characterization of MTAP‐Deficient Metastatic Urothelial Cancer,” European Urology Oncology 6, no. 2 (2023): 228–232.
C. F. Gaspar, N. Y. Ngoi, T. Tang, et al., “Abstract 963: Clinical Impact of MTAP Status in Advanced Cholangiocarcinoma: Genomic Profile and Response to Treatment,” Cancer Research 83, no. 7_Supplement (2023): 963.
D. Owen, R. Ben‐Shachar, J. Feliciano, et al., “Actionable Structural Variant Detection via RNA‐NGS and DNA‐NGS in Patients With Advanced Non‐Small Cell Lung Cancer,” JAMA Network Open 7, no. 11 (2024): e2442970.
J. Buckley, R. J. Schmidt, D. Ostrow, et al., “An Exome Capture‐Based RNA‐Sequencing Assay for Genome‐Wide Identification and Prioritization of Clinically Important Fusions in Pediatric Tumors,” Journal of Molecular Diagnostics 26, no. 2 (2024): 127–139.
K. Marjon, M. J. Cameron, P. Quang, et al., “MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis,” Cell Reports 15, no. 3 (2016): 574–587.
M. M. Fischer, K. Gerrick, B. Belmontes, et al., “Abstract 1644: Dual Inhibition of MAT2A and PRMT5 Delivers Synergistic Anti‐Tumor Responses in Preclinical Models of MTAP‐Deleted Cancer,” Cancer Research 83, no. 7_Supplement (2023): 1644.
B. Subramaniam, B. Kritzer, E. Putnam, et al., “HGG‐02. Metabolic Targeting of High‐Grade Gliomas With MTAP Loss,” Neuro‐Oncology 25, no. Supplement_1 (2023): i38.
G. Gao, L. Zhang, O. D. Villarreal, et al., “PRMT1 Loss Sensitizes Cells to PRMT5 Inhibition,” Nucleic Acids Research 47, no. 10 (2019): 5038–5048.
G. T. Bedard, N. Gilaj, K. Peregrina, et al., “Combined Inhibition of MTAP and MAT2a Mimics Synthetic Lethality in Tumor Models via PRMT5 Inhibition,” Journal of Biological Chemistry 300, no. 1 (2024): 105492.
C. L. Neilan, M. M. Fischer, D. Garbett, et al., “Abstract B027: The MAT2A Inhibitor IDE397: A Novel Combination Backbone for Urothelial Cancer Subjects With MTAP Deficiency,” Clinical Cancer Research 30, no. 10_Supplement (2024): B027–B.
P. A. Shah, A. K. Saw, W. Padron, et al., “Abstract 4536: MTAP Loss Alters the Epigenetic Landscape and Demonstrates Superior Therapeutic Sensitivity to Concomitant PRMT5 and PARP Inhibition in Cholangiocarcinoma,” Cancer Research 84, no. 6_Supplement (2024): 4536.
Grant Information:
82102777 National Natural Science Foundation of China
Contributed Indexing:
Keywords: MTAP rearrangement; clinical characteristics; pediatric acute lymphoblastic leukemia; prognosis; whole‐transcriptome sequencing
Substance Nomenclature:
0 (Biomarkers, Tumor)
Entry Date(s):
Date Created: 20251120 Date Completed: 20260127 Latest Revision: 20260127
Update Code:
20260130
DOI:
10.1002/mpo.70012
PMID:
41261957
Database:
MEDLINE
*Further Information*
*Objective: To investigate the distribution and molecular characteristics of MTAP rearrangements in pediatric acute lymphoblastic leukemia (ALL) and assess their impact on clinical features, treatment response, and prognosis.
Methods: We retrospectively analyzed 338 pediatric ALL patients. Patients were stratified into two cohorts based on MTAP rearrangement status: the MTAP-r group and the non-MTAP-r group. Baseline clinical characteristics, molecular profiles, and induction therapy responses were compared between the groups. Prognostic outcomes were also evaluated.
Results: Among the 338 pediatric ALL patients, 32 (9.47%) harbored MTAP rearrangements. Compared to the non-MTAP-r group, patients in the MTAP-r group demonstrated a significantly higher proportion of T-ALL (p < 0.05), elevated peripheral WBC counts at diagnosis, higher LDH levels, and were more frequently classified into intermediate-/high-risk groups (p < 0.05). Five distinct MTAP rearrangement patterns were identified, with MTAP::CDKN2B-AS1 being the most prevalent (75.0%). Regarding mutational profiles, MTAP-r patients exhibited a higher frequency of mutations in NOTCH1, PTEN, FBXW7, SRCAP, and USP7. Furthermore, the mutated genes were significantly enriched in pathways related to viral carcinogenesis, immune evasion, and metabolic signaling. Patients with MTAP-r ALL exhibited significantly inferior outcomes compared to those in the non-MTAP-r group.
Conclusion: MTAP rearrangement defines a distinct and clinically adverse subset of pediatric ALL characterized by specific fusion architecture and an unfavorable co-mutation pattern. Beyond its diagnostic value, MTAP-r represents a promising biomarker for trial enrollment and future risk-adapted strategies. Confirmation of independent prognostic impact and therapeutic utility will require multivariable analyses and prospective, biomarker-driven studies.
(© 2025 Wiley Periodicals LLC.)*