{"doi":"10.1002/ajh.25991","title":"Natural history of newly diagnosed myelodysplastic syndrome with isolated inv(3)/t(3;3)","abstract":"The MDS1 and EVI1 complex locus (MECOM) rearrangements inv(3) and t(3;3) are adverse cytogenetic abnormalities observed in less than 1% of patients with myelodysplastic syndrome (MDS), and are associated with a high risk for progression to acute myeloid leukemia (AML).1, 2 Both inv(3) and t(3;3) occur within the MECOM complex at genes EVI1 and MDS1 on chromosome 3q26.2 and the RPN1 and GATA2 genes on chromosome 3q21.2 These rearrangements result in overexpression of the oncogenic transcription factor EVI1: EVI1/RPN1 fusion or a longer variant at the MDS1/EVI1 transcript.3 Such overexpression can promote proliferation and impair differentiation of myeloid precursor cells, which leads to leukemogenesis. Given the unique biological process and poor prognosis associated with the MECOM rearrangements, we hypothesized that the presence of inv(3)/t(3;3) warrant a diagnosis of AML regardless of the percentage of blasts in bone marrow. However, MECOM rearrangements are often accompanied with other adverse karyotype abnormalities such as monosomy 7.4, 5 Therefore, the purpose of this study is to evaluate clinical course of patients with MDS and isolated inv(3)/t(3;3). We performed a cytogenetic database search of patients admitted to MD Anderson Cancer Center with MDS and AML from 24 November 1997 to 2 February 2020 for the presence of isolated inv(3) and t(3;3). Patients who had other chromosomal abnormalities at initial diagnosis of MDS other than inv(3) and t(3;3) were excluded from further analysis, as were those who previously received hypomethylating agents (HMAs), cytarabine-based regimens, or intensive chemotherapy. The International Working Group 2006 criteria were used for treatment response evaluation. Complete remission (CR) was defined as <5% blasts with normal maturation of all cell lines, hemoglobin level >11 g/dL, absolute neutrophil count >1 × 109/L, platelet count >100 × 109/L, and 0% blasts in peripheral blood smears. Bone marrow aspirates from patients with newly diagnosed or therapy-related MDS were analyzed via conventional karyotyping and next generation sequencing. We compared the outcome of patients with MDS and isolated inv(3)/t(3;3) to patients with newly diagnosed AML and isolated inv(3)/t(3;3). The 2017 European LeukemiaNet recommendations were used for treatment response evaluation in AML patients. Complete remission was defined as <5% blasts in bone marrow, absence of Auer rods and extramedullary disease, absolute neutrophil count >1 × 109/L, platelet count >100 × 109/L, and absence of blasts in peripheral blood. Outcomes of chemotherapy (HMAs, cytarabine-based regimens, intensive therapy) and allogeneic stem cell transplantation (ASCT) were reviewed. Progression to AML was defined as the presence of ≥20% blasts in bone marrow or peripheral blood following an initial diagnosis of MDS. Baseline patient characteristics were compared with the Fisher's exact, Mann-Whitney U, and chi-square tests to assess differences between patients with MDS and isolated inv(3)/t(3;3) and patients with AML and inv(3)/t(3;3). Progression-free survival (PFS) was measured from the date of diagnosis to the date of progression from MDS to AML, death, or last follow-up; overall survival (OS) was measured from the date of diagnosis to the date of death or last follow-up visit. The Kaplan-Meier method was used to estimate PFS and OS, and was compared by a log-rank test. All reported P values were two-sided, and P values <.05 were considered significant. All statistical analyses were performed using the SPSS software program (version 24). We reviewed 441 bone marrow aspirates with either inv(3) or t(3;3) from 161 patients [inv(3), 182 bone marrow samples from 78 patients; t(3;3), 259 bone marrow samples from 83 patients]. We identified 15 patients with newly diagnosed MDS and either isolated inv(3) or isolated t(3;3) (Figure 1; Table S1; Table S2; Table S3). By IPSS, six patients (40%) were in the intermediate-1, six patients (40%) we","journal":"American Journal of Hematology","year":2020,"id":107515,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232846,"name":"Guillermo Montalban‐Bravo","orcid":"0000-0002-4533-5176","position":1,"is_corresponding":false},{"id":250530,"name":"Rashmi Kanagal‐Shamanna","orcid":"0000-0001-7829-5249","position":2,"is_corresponding":false},{"id":230404,"name":"Elias Jabbour","orcid":"0000-0003-4465-6119","position":3,"is_corresponding":false},{"id":230403,"name":"Farhad Ravandi","orcid":"0000-0002-7621-377X","position":4,"is_corresponding":false},{"id":232841,"name":"Tapan M. Kadia","orcid":"0000-0002-9892-9832","position":5,"is_corresponding":false},{"id":232840,"name":"Naval Daver","orcid":"0000-0001-7103-373X","position":6,"is_corresponding":false},{"id":232838,"name":"Naveen Pemmaraju","orcid":"0000-0002-1670-6513","position":7,"is_corresponding":false},{"id":18373,"name":"Marina Konopleva","orcid":"0000-0002-9347-2212","position":8,"is_corresponding":false},{"id":232842,"name":"Gautam Borthakur","orcid":"0000-0001-7679-6453","position":9,"is_corresponding":false},{"id":108815,"name":"Koichi Takahashi","orcid":"0000-0002-8027-9659","position":10,"is_corresponding":false},{"id":33069,"name":"Keyur P. Patel","orcid":"0000-0001-5081-2427","position":11,"is_corresponding":false},{"id":264721,"name":"Kelly A. Soltysiak","orcid":"0000-0001-6113-3745","position":12,"is_corresponding":false},{"id":264720,"name":"Kelly S. Chien","orcid":"0000-0001-6024-1613","position":13,"is_corresponding":false},{"id":516595,"name":"Kenichi Sakurai","orcid":"0000-0002-7056-2151","position":14,"is_corresponding":false},{"id":280568,"name":"Sherry Pierce","orcid":"0000-0002-9542-1558","position":15,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":16,"is_corresponding":false},{"id":230408,"name":"Guillermo Garcia‐Manero","orcid":"0000-0002-3631-2482","position":17,"is_corresponding":false},{"id":232853,"name":"Koji Sasaki","orcid":"0000-0002-9140-0610","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-18T23:12:34.898963Z","pmid":"32886803","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}