{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:30:58Z","timestamp":1782307858399,"version":"3.54.5"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background: Acute myeloid leukemia (AML) with CBFB::MYH11 fusion and myeloid\/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are genetically defined and typically mutually exclusive entities. Case Presentation: We report a unique case of de novo AML harboring two clonal, transcriptionally active class-defining fusions: CBFB::MYH11 and GOLGA4::PDGFRB. A 61-year-old woman presented with leukocytosis with neutrophilia, eosinophilia, and monocytosis; circulating blasts; and a markedly hypercellular marrow. Cytogenetic analysis revealed inv(16)(p13.1q22) and t(3;5)(p21;q32) in all 20 metaphases, and RNA sequencing confirmed expression of both CBFB::MYH11 and GOLGA4::PDGFRB fusions. In addition, an oncogenic WT1 frameshift variant was identified. Hematopathologic findings were largely consistent with AML with CBFB::MYH11 fusion but exhibited features reminiscent of PDGFRB-rearranged MLN-TK. The patient achieved complete remission following the standard 7 + 3 induction chemotherapy regimen for AML with gemtuzumab ozogamicin. Conclusions: This case illustrates the diagnostic challenges posed by concomitant class-defining alterations in hematologic neoplasms and underscores the importance of integrated genomic assessment.<\/jats:p>","DOI":"10.3390\/hematolrep18020024","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Concomitant Clonal CBFB::MYH11 and PDGFRB Fusions in a Case of De Novo Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"18","author":[{"given":"Qiliang","family":"Ding","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-7114","authenticated-orcid":false,"given":"Natasha E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-6181","authenticated-orcid":false,"given":"Cody J.","family":"Artymiuk","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"He","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhett P.","family":"Ketterling","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Viswanatha","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5536-9011","authenticated-orcid":false,"given":"Patricia T.","family":"Greipp","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-4965","authenticated-orcid":false,"given":"Cinthya J.","family":"Zepeda Mendoza","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pulikkan, J.A., and Castilla, L.H. (2018). Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00129"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/ajh.24710","article-title":"Myeloid neoplasms with concurrent BCR-ABL1 and CBFB rearrangements: A series of 10 cases of a clinically aggressive neoplasm","volume":"92","author":"Salem","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1182\/blood.2023022417","article-title":"How I diagnose and treat myeloid\/lymphoid neoplasms with tyrosine kinase gene fusions","volume":"145","author":"Reiter","year":"2025","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41417-019-0147-1","article-title":"The incidence, genetic characteristics, and prognosis of leukemia with concurrent pathogenic fusion genes: A series of 25 cases from a large cohort of leukemia patients","volume":"27","author":"Chen","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Saxe, D.F., May, K.M., and Priest, J.H. (2017). General cell culture principles and fibroblast culture. The AGT Cytogenetics Laboratory Manual, John Wiley & Sons, Inc.","DOI":"10.1002\/9781119061199.ch4"},{"key":"ref_9","first-page":"S51","article-title":"Clinical Validation of a Targeted RNA Sequencing Panel for Gene Fusions and Select Relative Gene Expression in Hematologic Malignancies","volume":"27","author":"Artymiuk","year":"2025","journal-title":"J. Mol. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1093\/bioinformatics\/btab249","article-title":"MetaFusion: A high-confidence metacaller for filtering and prioritizing RNA-seq gene fusion candidates","volume":"37","author":"Apostolides","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1101\/gr.257246.119","article-title":"Accurate and efficient detection of gene fusions from RNA sequencing data","volume":"31","author":"Uhrig","year":"2021","journal-title":"Genome Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Haas, B., Dobin, A., Stransky, N., Li, B., Yang, X., Tickle, T., Bankapur, A., Ganote, C., Doak, T., and Pochet, N. (2017). STAR-Fusion: Fast and Accurate Fusion Transcript Detection from RNA-Seq. bioRxiv.","DOI":"10.1101\/120295"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kalari, K.R., Nair, A.A., Bhavsar, J.D., O\u2019Brien, D.R., Davila, J.I., Bockol, M.A., Nie, J., Tang, X., Baheti, S., and Doughty, J.B. (2014). MAP-RSeq: Mayo Analysis Pipeline for RNA sequencing. BMC Bioinform., 15.","DOI":"10.1186\/1471-2105-15-224"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/ng.3466","article-title":"Exploring genomic alteration in pediatric cancer using ProteinPaint","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1242\/jcs.02358","article-title":"tGolgin-1 (p230, golgin-245) modulates Shiga-toxin transport to the Golgi and Golgi motility towards the microtubule-organizing centre","volume":"118","author":"Yoshino","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.bbrc.2014.11.071","article-title":"Trans-Golgi protein p230\/golgin-245 is involved in phagophore formation","volume":"456","author":"Sohda","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D780","DOI":"10.1093\/nar\/gky1020","article-title":"Haemopedia RNA-seq: A database of gene expression during haematopoiesis in mice and humans","volume":"47","author":"Choi","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.critrevonc.2016.11.008","article-title":"Platelet-derived growth factor receptors (PDGFRs) fusion genes involvement in hematological malignancies","volume":"109","author":"Lan","year":"2017","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1365-2141.2009.07955.x","article-title":"Fusion of PDGFRB to two distinct loci at 3p21 and a third at 12q13 in imatinib-responsive myeloproliferative neoplasms","volume":"148","author":"Apperley","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1038\/s41417-023-00651-w","article-title":"A novel subclonal rearrangement of the STRN3::PDGFRB gene in de novo acute myeloid leukemia with NPM1 mutation and its leukemogenic effects","volume":"30","author":"Wang","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/jha2.895","article-title":"Concurrent BCR-ABL1 and core binding factor beta rearrangement in de novo acute myeloid leukemia: A case report and review of literature","volume":"5","author":"Salter","year":"2024","journal-title":"EJHaem"},{"key":"ref_22","first-page":"8822670","article-title":"De Novo Acute Myeloid Leukemia with Combined CBFB-MYH11 and BCR-ABL1 Gene Rearrangements: A Case Report and Review of Literature","volume":"2020","author":"Sethapati","year":"2020","journal-title":"Case Rep. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.5045\/br.2014.49.1.22","article-title":"Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities","volume":"49","author":"Han","year":"2014","journal-title":"Blood Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cancergen.2025.08.004","article-title":"Unfavorable disease progression in patients with chronic myeloid leukemia and concurrent t(6;9) translocation (DEK::NUP214 fusion) or inversion 16 (CBFB::MYH11 fusion)","volume":"298\u2013299","author":"Zhang","year":"2025","journal-title":"Cancer Genet."},{"key":"ref_25","first-page":"103175","article-title":"The epigenetic landscape of acute myeloid leukemia","volume":"2014","author":"Prideaux","year":"2014","journal-title":"Adv. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3324\/haematol.2015.141796","article-title":"Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia","volume":"101","author":"Rampal","year":"2016","journal-title":"Haematologica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1182\/blood-2024-199066","article-title":"Prognostic Significance of Wilms\u2019 Tumor 1 Gene Mutations in Acute Myeloid Leukemia: Risk Stratification and Survival Outcomes","volume":"144","author":"Ugale","year":"2024","journal-title":"Blood"}],"container-title":["Hematology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/2\/24\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:28:05Z","timestamp":1774261685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/2\/24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["hematolrep18020024"],"URL":"https:\/\/doi.org\/10.3390\/hematolrep18020024","relation":{},"ISSN":["2038-8330"],"issn-type":[{"value":"2038-8330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]}}}