{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:18:24Z","timestamp":1769559504703,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background and Clinical Significance: Acute promyelocytic leukemia (APL) is a rapidly progressive subtype of acute myeloid leukemia defined by PML::RARA fusion and characterized by life-threatening coagulopathy. Because the disease typically follows an aggressive course, immediate treatment is essential once APL is suspected. This case report describes an atypical de novo presentation marked by indolent progression rather than the expected aggressive trajectory. Case Presentation: A 37-year-old female exhibited gradually declining white blood cell and neutrophil counts over the course of a year, followed by unexplained pancytopenia with severe neutropenia (0.1 \u00d7 109\/L). Evaluation for nutritional deficiencies and autoimmune disease was unrevealing aside from a positive ANA without clinical features of autoimmunity. Bone-marrow biopsy demonstrated morphologic and flow cytometric findings suggestive of APL, low-level t(15;17), PML::RARA fusion, and concomitant TP53 loss and ETV6 mutation. Despite the indolent clinical presentation and low disease burden, the molecular and cytogenetic findings confirmed the diagnosis of classical APL with TP53 loss and ETV6 mutation. Induction therapy with all-trans-retinoic acid and arsenic trioxide resulted in hematologic remission. Conclusions: This case highlights an unusually indolent form of de novo APL not previously documented in the literature, expanding the recognized clinical spectrum of the disease. The findings emphasize the importance of still considering severe diagnoses, such as APL, when presentations deviate from classical patterns. Atypical clinical trajectories should prompt careful assessment of marrow morphology and immunophenotypic features. Continued characterization of such cases may refine diagnostic criteria and direct individualized approaches to therapy.<\/jats:p>","DOI":"10.3390\/hematolrep18010012","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:35:42Z","timestamp":1769513742000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Primary Indolent Acute Promyelocytic Leukemia"],"prefix":"10.3390","volume":"18","author":[{"given":"Breanne","family":"Wolfenbarger","sequence":"first","affiliation":[{"name":"Alabama College of Osteopathic Medicine, Dothan, AL 36303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5298-5110","authenticated-orcid":false,"given":"Daley","family":"Morera","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandol","family":"Wolfenbarger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Jillella","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology and Oncology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","first-page":"178","article-title":"Acute Promyelocytic Leukemia: A Summary","volume":"9","author":"Ryan","year":"2018","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_2","unstructured":"Cingam, S.R., and Koshy, N.V. (2023). Acute Promyelocytic Leukemia. StatPearls, StatPearls Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41408-021-00514-3","article-title":"Acute promyelocytic leukemia current treatment algorithms","volume":"11","author":"Yilmaz","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_4","unstructured":"National Cancer Institute (2025, December 30). Surveillance, Epidemiology, and End Results Program (SEER). Cancer Stat Facts: Leukemia\u2014Acute Myeloid Leukemia (AML), Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/amyl.html."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Woods, A.C., and Norsworthy, K.J. (2023). Differentiation Syndrome in Acute Leukemia: APL and Beyond. Cancers, 15.","DOI":"10.3390\/cancers15194767"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/ajh.1073","article-title":"CD34-positive acute promyelocytic leukemia is associated with leukocytosis, microgranular\/hypogranular morphology, expression of CD2 and bcr3 isoform","volume":"67","author":"Foley","year":"2001","journal-title":"Am. J. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/sj.leu.2404412","article-title":"Flow cytometry analysis of acute promyelocytic leukemia: The power of \u2018surface hematology\u2019","volume":"21","author":"Mirabelli","year":"2007","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ally, F., and Chen, X. (2024). Acute Myeloid Leukemia: Diagnosis and Evaluation by Flow Cytometry. Cancers, 16.","DOI":"10.3390\/cancers16223855"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/ccr3.2686","article-title":"Acute promyelocytic leukemia presenting with atypical basophils","volume":"8","author":"Shameli","year":"2020","journal-title":"Clin. Case Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"992","DOI":"10.18632\/oncotarget.27513","article-title":"Acute promyelocytic leukemia (APL): A review of the literature","volume":"11","author":"Jimenez","year":"2020","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.5858\/arpa.2013-0345-RS","article-title":"Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations","volume":"139","author":"Adams","year":"2015","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hermsen, J., and Hambley, B. (2023). The Coagulopathy of Acute Promyelocytic Leukemia: An Updated Review of Pathophysiology, Risk Stratification, and Clinical Management. Cancers, 15.","DOI":"10.3390\/cancers15133477"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Geoffroy, M.C., and de Th\u00e9, H. (2020). Classic and Variants APLs, as Viewed from a Therapy Response. Cancers, 12.","DOI":"10.3390\/cancers12040967"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a026260","DOI":"10.1101\/cshperspect.a026260","article-title":"p53 as an Effector or Inhibitor of Therapy Response","volume":"6","author":"Ablain","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_15","first-page":"8","article-title":"Acute promyelocytic leukemia with JAK2 V617F and severe differentiation syndrome","volume":"4","author":"Braun","year":"2014","journal-title":"Leuk. Res. Rep."},{"key":"ref_16","first-page":"100243","article-title":"Acute promyelocyte leukemia arose from CALR 1 mutated post essential thrombocythemia\u2014Myelofibrosis with splanchnic vein thrombosis: A case report","volume":"15","author":"Morsia","year":"2021","journal-title":"Leuk Res. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.21037\/sci.2016.03.02","article-title":"Acute promyelocytic leukemia co-existing with JAK2 V617F positive myeloproliferative neoplasm: A case report","volume":"3","author":"Wu","year":"2016","journal-title":"Stem Cell Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/gcc.2870100104","article-title":"Myelodysplastic syndrome transforming to acute promyelocytic-like leukemia with trisomy and rearrangement of chromosome 11","volume":"10","author":"Najfeld","year":"1994","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1159\/000328997","article-title":"Acute promyelocytic leukemia with a smoldering course associated with therapy-related myelodysplastic syndrome","volume":"126","author":"Wolach","year":"2011","journal-title":"Acta Haematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3343\/alm.2021.41.3.328","article-title":"Promyelocytic Blast Phase of Chronic Myeloid Leukemia, BCR-ABL1-Positive: Points to be Considered at Diagnosis","volume":"41","author":"Kim","year":"2021","journal-title":"Ann. Lab. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1159\/000534862","article-title":"An Acute Promyelocytic Leukemia Resistant to All-Trans Retinoic Acid: A Case Report of the ZBTB16::RARa Variant and Review of the Literature","volume":"16","author":"Castelijn","year":"2023","journal-title":"Case Rep. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.3892\/ol.2016.4544","article-title":"Significance of ETV6 rearrangement in acute promyelocytic leukemia with t(15;17)\/promyelocytic leukemia\/retinoic acid receptor alpha","volume":"11","author":"Gao","year":"2016","journal-title":"Oncol. Lett."}],"container-title":["Hematology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/1\/12\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:49:30Z","timestamp":1769514570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/1\/12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["hematolrep18010012"],"URL":"https:\/\/doi.org\/10.3390\/hematolrep18010012","relation":{},"ISSN":["2038-8330"],"issn-type":[{"value":"2038-8330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]}}}