{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:58:22Z","timestamp":1760147902582,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health, National Cancer Institute COG","award":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"],"award-info":[{"award-number":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"]}]},{"name":"St Baldrick\u2019s Foundation","award":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"],"award-info":[{"award-number":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"]}]},{"name":"National Institutes of Health, National Cancer Institute","award":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"],"award-info":[{"award-number":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"]}]},{"name":"Takeda Pharmaceuticals","award":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"],"award-info":[{"award-number":["U10 CA98543","U10 CA98413","U10 CA180886","1U24-CA196173","U10 CA180899","R01-CA164024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DNA damage response (DNADR) recognition and repair (DDR) pathways affect carcinogenesis and therapy responsiveness in cancers, including leukemia. We measured protein expression levels of 16 DNADR and DDR proteins using the Reverse Phase Protein Array methodology in acute myeloid (AML) (n = 1310), T-cell acute lymphoblastic leukemia (T-ALL) (n = 361) and chronic lymphocytic leukemia (CLL) (n = 795) cases. Clustering analysis identified five protein expression clusters; three were unique compared to normal CD34+ cells. Individual protein expression differed by disease for 14\/16 proteins, with five highest in CLL and nine in T-ALL, and by age in T-ALL and AML (six and eleven proteins, respectively), but not CLL (n = 0). Most (96%) of the CLL cases clustered in one cluster; the other 4% were characterized by higher frequencies of deletion 13q and 17p, and fared poorly (p &lt; 0.001). T-ALL predominated in C1 and AML in C5, but both occurred in all four acute-dominated clusters. Protein clusters showed similar implications for survival and remission duration in pediatric and adult T-ALL and AML populations, with C5 doing best in all. In summary, DNADR and DDR protein expression was abnormal in leukemia and formed recurrent clusters that were shared across the leukemias with shared prognostic implications across diseases, and individual proteins showed age- and disease-related differences.<\/jats:p>","DOI":"10.3390\/ijms24065460","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T06:52:13Z","timestamp":1678690333000},"page":"5460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reverse Phase Protein Array Profiling Identifies Recurrent Protein Expression Patterns of DNA Damage-Related Proteins across Acute and Chronic Leukemia: Samples from Adults and the Children\u2019s Oncology Group"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-1255","authenticated-orcid":false,"given":"Fieke W.","family":"Hoff","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-9030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4227-3870","authenticated-orcid":false,"given":"Ti\u2019ara L.","family":"Griffen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310-1458, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon D.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-4242","authenticated-orcid":false,"given":"Terzah M.","family":"Horton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX 77030-3498, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Wierda","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-4393","authenticated-orcid":false,"given":"Stefan E.","family":"Hubner","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihua","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-9548","authenticated-orcid":false,"given":"Steven M.","family":"Kornblau","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ajh.26156","article-title":"Acute lymphoblastic leukemia: A population-based study of outcome in the United States based on the surveillance, epidemiology, and end results (SEER) database, 1980\u20132017","volume":"96","author":"Sasaki","year":"2021","journal-title":"Am. 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