دورية أكاديمية
Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia.
| العنوان: | Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia. |
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| المؤلفون: | Spitzer B; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Pediatrics, Weill Cornell Medical College, New York, New York., Rutherford KD; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., Gundem G; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., McGovern EM; Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York., Millard NE; Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington., Arango Ossa JE; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., Cheung IY; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Gao T; Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, Massachusetts., Levine MF; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., Zhang Y; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Medina-Martínez JS; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., Feng Y; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Ptashkin RN; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Bolton KL; Division of Oncology, Department of Medicine, Washington University, St. Louis, Missouri., Farnoud N; Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York., Zhou Y; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., Patel MA; Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York., Asimomitis G; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York., Cobbs CC; Integrated Genomics Core, Memorial Sloan Kettering Cancer Center, New York, New York., Mohibullah N; Integrated Genomics Core, Memorial Sloan Kettering Cancer Center, New York, New York., Huberman KH; Integrated Genomics Core, Memorial Sloan Kettering Cancer Center, New York, New York., Arcilla ME; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Kushner BH; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Modak S; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Kung AL; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Zehir A; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Levine RL; Human Oncology and Oncogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York., Armstrong SA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Cheung NKV; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Papaemmanuil E; Center for Computational Oncology, Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, New York, New York. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Apr 14; Vol. 28 (8), pp. 1614-1627. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Cancer Survivors* , Leukemia, Myeloid, Acute*/genetics , Neuroblastoma*/pathology, Adult ; Bone Marrow/pathology ; Child ; Clone Cells ; Humans |
| مستخلص: | Purpose: Therapy-related myelodysplastic syndrome and acute leukemias (t-MDS/AL) are a major cause of nonrelapse mortality among pediatric cancer survivors. Although the presence of clonal hematopoiesis (CH) in adult patients at cancer diagnosis has been implicated in t-MDS/AL, there is limited published literature describing t-MDS/AL development in children. Experimental Design: We performed molecular characterization of 199 serial bone marrow samples from 52 patients treated for high-risk neuroblastoma, including 17 with t-MDS/AL (transformation), 14 with transient cytogenetic abnormalities (transient), and 21 without t-MDS/AL or cytogenetic alterations (neuroblastoma-treated control). We also evaluated for CH in a cohort of 657 pediatric patients with solid tumor. Results: We detected at least one disease-defining alteration in all cases at t-MDS/AL diagnosis, most commonly TP53 mutations and KMT2A rearrangements, including involving two novel partner genes (PRDM10 and DDX6). Backtracking studies identified at least one t-MDS/AL-associated mutation in 13 of 17 patients at a median of 15 months before t-MDS/AL diagnosis (range, 1.3-32.4). In comparison, acquired mutations were infrequent in the transient and control groups (4/14 and 1/21, respectively). The relative risk for development of t-MDS/AL in the presence of an oncogenic mutation was 8.8 for transformation patients compared with transient. Unlike CH in adult oncology patients, TP53 mutations were only detectable after initiation of cancer therapy. Last, only 1% of pediatric patients with solid tumor evaluated had CH involving myeloid genes. Conclusions: These findings demonstrate the clinical relevance of identifying molecular abnormalities in predicting development of t-MDS/AL and should guide the formation of intervention protocols to prevent this complication in high-risk pediatric patients. (©2022 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | K08 CA241318 United States CA NCI NIH HHS; P01 CA066996 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01 CA176745 United States CA NCI NIH HHS |
| تواريخ الأحداث: | Date Created: 20220126 Date Completed: 20220415 Latest Revision: 20240430 |
| رمز التحديث: | 20240430 |
| مُعرف محوري في PubMed: | PMC9983778 |
| DOI: | 10.1158/1078-0432.CCR-21-2451 |
| PMID: | 35078859 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-21-2451 |