{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:25:46Z","timestamp":1760059546016,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The biology of Monosomal Karyotype Acute Myeloid Leukemia (MK AML) remains unclear, and its mutational profile has not been exclusively assessed. We sought to determine the genomic profile of MK AML patients and its correlation with overall survival (OS). We conducted a retrospective study involving 664 AML patients, identifying 156 (23.5%) with MK AML. The most common monosomies were -17 (41%) and -7 (37%), with 149 (95%) and 138 (88%) having myelodysplasia-related (MR) cytogenetics and complex karyotype (CK), respectively. Frequent mutations included TP53 (69%), DNMT3A (19%), TET2 (13%), and IDH1 (7%). Patients with MK AML with TP53 mutation (TP53 Mut) had shorter OS compared to those with TP53 wild-type (WT) (median OS, 3.9 versus 9.2 months, p = 0.002). Our validation study further supports this finding. There was no significant difference in OS related to the presence or absence of CK (p = 0.252), MR mutations (p = 0.252), DNMT3A (p = 0.264), TET2 (p = 0.264), and IDH1 (p = 0.183) alterations. Co-mutation with novel EPI6 and TAZI signature alterations did not significantly impact OS among MK AML TP53 Mut patients, suggesting that TP53 Mut remains the dominant driver of outcome in this subgroup. In conclusion, MK AML is a genotypically diverse and high-risk group, with MK AML TP53 Mut indicating worse prognosis.<\/jats:p>","DOI":"10.3390\/ijms26125845","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T09:36:00Z","timestamp":1750239360000},"page":"5845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic Profile and Clinical Outcomes in Acute Myeloid Leukemia with Monosomal Karyotype"],"prefix":"10.3390","volume":"26","author":[{"given":"Collins","family":"Wangulu","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Biobank (PMCB), University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1V4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9518-9879","authenticated-orcid":false,"given":"Ehsan","family":"Bahrami Hezaveh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Hematology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojgan","family":"Zarif","sequence":"additional","affiliation":[{"name":"Department of Laboratory Hematology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7483-0478","authenticated-orcid":false,"given":"Qianghua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1V4, Canada"},{"name":"Department of Laboratory Hematology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winnie","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1V4, Canada"},{"name":"Laboratory Medicine Program, Clinical Laboratory Genetics, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuihong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1V4, Canada"},{"name":"Laboratory Medicine Program, Clinical Laboratory Genetics, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-8583","authenticated-orcid":false,"given":"Hassan","family":"Sibai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1V4, Canada"},{"name":"Department of Laboratory Hematology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.2147\/OTT.S133937","article-title":"Monosomal Karyotype in Myeloid Neoplasias: A Literature Review","volume":"10","author":"Anelli","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1182\/blood-2010-02-270330","article-title":"Prognostic Impact of Monosomal Karyotype in Young Adult and Elderly Acute Myeloid Leukemia: The Southwest Oncology Group (SWOG) Experience","volume":"116","author":"Medeiros","year":"2010","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1056\/NEJMoa0901409","article-title":"High-Dose Daunorubicin in Older Patients with Acute Myeloid Leukemia","volume":"361","author":"Ossenkoppele","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1200\/JCO.2008.16.0259","article-title":"Monosomal Karyotype in Acute Myeloid Leukemia: A Better Indicator of Poor Prognosis than a Complex Karyotype","volume":"26","author":"Breems","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1309\/AJCPMLO84JDNVLNK","article-title":"Acute Myeloid Leukemia with Monosomal Karyotype: Morphologic, Immunophenotypic, and Molecular Findings","volume":"142","author":"Weinberg","year":"2014","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cancergen.2012.10.003","article-title":"Monosomal Karyotype in Acute Myeloid Leukemia Defines a Distinct Subgroup within the Adverse Cytogenetic Risk Category","volume":"206","author":"Voutiadou","year":"2013","journal-title":"Cancer Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1182\/blood-2011-07-367508","article-title":"Monosomal Karyotype in Adult Acute Myeloid Leukemia: Prognostic Impact and Outcome after Different Treatment Strategies","volume":"119","author":"Kayser","year":"2012","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3324\/haematol.2015.132654","article-title":"Monosomal Karyotype as an Adverse Prognostic Factor in Patients with Acute Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem-Cell Transplantation in First Complete Remission: A Retrospective Survey on Behalf of the Alwp of the Ebmt","volume":"101","author":"Labopin","year":"2016","journal-title":"Haematologica"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and Management of AML in Adults: 2022 Recommendations from an International Expert Panel on Behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.7314\/APJCP.2012.13.11.5421","article-title":"Monosomal Karyotypes among 1147 Chinese Patients with Acute Myeloid Leukemia: Prevalence, Features and Prognostic Impact","volume":"13","author":"Yang","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3109\/10428194.2011.608453","article-title":"Monosomal Karyotype Routinely Defines a Poor Prognosis Subgroup in Acute Myeloid Leukemia and Is Frequently Associated with TP53 Deletion","volume":"53","author":"Gaillard","year":"2012","journal-title":"Leuk. Lymphoma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ajh.25469","article-title":"Distinct Mutation Spectrum, Clinical Outcome and Therapeutic Responses of Typical Complex\/Monosomy Karyotype Acute Myeloid Leukemia Carrying TP53 Mutations","volume":"94","author":"Leung","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1182\/blood-2011-08-375758","article-title":"TP53 Alterations in Acute Myeloid Leukemia with Complex Karyotype Correlate with Specific Copy Number Alterations, Monosomal Karyotype, and Dismal Outcome","volume":"119","author":"Schlenk","year":"2012","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41586-018-0623-z","article-title":"Functional Genomic Landscape of Acute Myeloid Leukaemia","volume":"562","author":"Tyner","year":"2018","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.clml.2013.07.009","article-title":"Prognostic Implications of Chromosome 17 Abnormalities in the Context of Monosomal Karyotype in Patients with Acute Myeloid Leukemia and Complex Cytogenetics","volume":"14","author":"Nazha","year":"2014","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/leu.2008.173","article-title":"TP53 Gene Mutation Is Frequent in Patients with Acute Myeloid Leukemia and Complex Karyotype, and Is Associated with Very Poor Prognosis","volume":"23","author":"Bowen","year":"2009","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000526174","article-title":"The Prognostic Value of TP53 Mutations in Adult Acute Myeloid Leukemia: A Meta-Analysis","volume":"50","author":"Qin","year":"2023","journal-title":"Transfus. Med. Hemother."},{"doi-asserted-by":"crossref","unstructured":"Shin, D.Y. (2023). TP53 Mutation in Acute Myeloid Leukemia: An Old Foe Revisited. Cancers, 15.","key":"ref_18","DOI":"10.3390\/cancers15194816"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1002\/cncr.30203","article-title":"TP53 Mutations in Newly Diagnosed Acute Myeloid Leukemia: Clinicomolecular Characteristics, Response to Therapy, and Outcomes","volume":"122","author":"Kadia","year":"2016","journal-title":"Cancer"},{"doi-asserted-by":"crossref","unstructured":"Bories, P., Prade, N., Lagarde, S., Cabarrou, B., Largeaud, L., Plenecassagnes, J., Luquet, I., de Mas, V., Filleron, T., and Cassou, M. (2020). Impact of TP53 Mutations in Acute Myeloid Leukemia Patients Treated with Azacitidine. PLoS ONE, 15.","key":"ref_20","DOI":"10.1371\/journal.pone.0238795"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41408-024-01186-5","article-title":"What Have We Learned about TP53- Mutated Acute Myeloid Leukemia?","volume":"14","author":"Shahzad","year":"2024","journal-title":"Blood Cancer J."},{"doi-asserted-by":"crossref","unstructured":"Zhao, D., Zarif, M., Zhou, Q., Capo-Chichi, J.M., Schuh, A., Minden, M.D., Atenafu, E.G., Kumar, R., and Chang, H. (2023). TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation. Cancers, 15.","key":"ref_22","DOI":"10.3390\/cancers15123210"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.1002\/cam4.5421","article-title":"Molecular Characterization of AML-MRC Reveals TP53 Mutation as an Adverse Prognostic Factor Irrespective of MRC-Defining Criteria, TP53 Allelic State, or TP53 Variant Allele Frequency","volume":"12","author":"Zhao","year":"2023","journal-title":"Cancer Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41408-024-01077-9","article-title":"Real World Predictors of Response and 24-Month Survival in High-Grade TP53-Mutated Myeloid Neoplasms","volume":"14","author":"Kaur","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/bjh.19895","article-title":"Somatic Co-Alteration Signatures Are Prognostic in High-Grade TP53-Mutated Myeloid Neoplasms","volume":"206","author":"Symes","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.1038\/s41467-022-32103-8","article-title":"Unified Classification and Risk-Stratification in Acute Myeloid Leukemia","volume":"13","author":"Tazi","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_27","first-page":"393","article-title":"Monosomal Karyotype among Adult Acute Myeloid Leukemia: Clinical Characteristic and Prognostic Analysis","volume":"35","author":"Feng","year":"2014","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1182\/bloodadvances.2021006239","article-title":"TP53 Mutation Defines a Unique Subgroup within Complex Karyotype de Novo and Therapy-Related MDS\/AML","volume":"6","author":"Weinberg","year":"2022","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/leu.2008.143","article-title":"Mutations of the TP53 Gene in Acute Myeloid Leukemia Are Strongly Associated with a Complex Aberrant Karyotype","volume":"22","author":"Haferlach","year":"2008","journal-title":"Leukemia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.ccell.2022.07.002","article-title":"Integrative Analysis of Drug Response and Clinical Outcome in Acute Myeloid Leukemia","volume":"40","author":"Bottomly","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106402","DOI":"10.1016\/j.leukres.2020.106402","article-title":"Acute Myeloid Leukemia or Myelodysplastic Syndrome with Chromosome 17 Abnormalities and Long-Term Outcomes with or without Hematopoietic Stem Cell Transplantation","volume":"95","author":"Britt","year":"2020","journal-title":"Leuk. Res."},{"doi-asserted-by":"crossref","unstructured":"Kang, D., Jung, J., Park, S., Cho, B.S., Kim, H.J., Kim, Y., Lee, J.M., Kim, H.S., Ahn, A., and Kim, M. (2022). Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes. J. Clin. Med., 11.","key":"ref_32","DOI":"10.3390\/jcm11092378"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1182\/blood.V126.23.564.564","article-title":"Clinical and Molecular Characterization of P53-Mutated Acute Myeloid Leukemia","volume":"126","author":"Kadia","year":"2015","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s12185-016-1942-1","article-title":"TP53 Mutations in Older Adults with Acute Myeloid Leukemia","volume":"103","author":"Yanada","year":"2016","journal-title":"Int. J. Hematol."},{"doi-asserted-by":"crossref","unstructured":"McGowan-Jordan, J., Simons, A., and Schmid, M. (2016). ISCN 2016: An International System for Human Cytogenomic Nomenclature (2016), Karger.","key":"ref_35","DOI":"10.1159\/isbn.978-3-318-06861-0"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1097\/HS9.0000000000000044","article-title":"Clinical Utility of Next-Generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience","volume":"2","author":"Alduaij","year":"2018","journal-title":"Hemasphere"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1182\/bloodadvances.2023011869","article-title":"A Real-World Analysis of Clinical Outcomes in AML with Myelodysplasia-Related Changes: A Comparison of ICC and WHO-HAEM5 Criteria","volume":"8","author":"Zhou","year":"2024","journal-title":"Blood Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5845\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:54:19Z","timestamp":1760032459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125845"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125845","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,6,18]]}}}