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Clinical, laboratory, cytogenetic, and mutational features are analyzed against an internal comparator cohort of JAK2-mutated chronic-phase PMF. Survival endpoints use Kaplan–Meier, log-rank tests, Cox regression, and multivariable logistic modeling for prognostic risk stratification.",{"@graph":69,"@context":127},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/triple-negative-primary-myelofibrosis-a-comparative-analysis-of-phenotype-genotype-and-outcome/441499/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/triple-negative-primary-myelofibrosis-a-comparative-analysis-of-phenotype-genotype-and-outcome/441499.png","ImageObject",300,407,{"name":92,"@type":93},"Damian","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What does “triple-negative” PMF mean in this study?","Question",{"text":113,"@type":114},"It refers to PMF cases in which routine mutation screening does not detect the canonical JAK2, CALR, or MPL driver mutations, operationally designated as “triple-negative MPN.” The study focuses on triple-negative PMF assigned by institutional mutation screening methods with specified analytic sensitivities.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were patients selected and what disease stage was excluded?",{"text":118,"@type":114},"Patients were retrospectively collected under an institutional review board–approved protocol. Diagnostic criteria followed the International Consensus Classification, with central review confirmation, and accelerated-phase PMF with PB/BM blasts ≥10% was excluded.",{"name":120,"@type":111,"acceptedAnswer":121},"Which statistical methods were used to evaluate prognosis and survival?",{"text":122,"@type":114},"Kaplan–Meier curves were built and compared using the log-rank test. Multivariable logistic regression adjusted for confounders, while Cox regression identified risk factors for overall survival (OS) and leukemia-free survival (LFS).",{"name":124,"@type":111,"acceptedAnswer":125},"What independent risk factors were identified for overall survival in triple-negative PMF?",{"text":126,"@type":114},"In multivariable OS analysis, independent risk factors included age >65 years, hemoglobin \u003C10 g/dL, leukocyte count >25 × 10^9/L, PB blasts ≥1%, and unfavorable karyotype.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},441499,1790794090,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149,"preview_page_count":4},137451208677,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj)  \nCORRESPONDENCE OPEN   \nTriple-negative primary myelofibrosis: a comparative analysis of phenotype, genotype, and outcome  \n© The Author(s) 2026  \nBlood Cancer Journal (2026)16:1; [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1038/s41408-025-01440-4](10.1038/s41408-025-01440-4)  \nDear Editor,  \nPrimary myelofibrosis (PMF), along with polycythemia vera (PV) and essential thrombocythemia (ET) constitute the three major myeloproliferative neoplasms (MPNs) that are characterized by somatic JAK2, CALR, or MPL mutations [1] . JAK2V617F or other JAK2 mutations occur in virtually all patients with PV [2] but their incidence is lower in ET and PMF with mutational frequencies of 50–60%[3, 4] . CALR and MPL mutations are rarely seen with PV but are detected in 20–30% and 3–7% of patients with ET [4], respectively, and in 25–30% and 5–7% of those with PMF [3] . It is now well established that these “MPN-driver mutations” might not be routinely detected in ~10–15% of patients with ET or PMF, operationally designated as “triple-negative MPN” [5] . Several studies have looked into triple-negative MPN in terms of underlying genomic alterations; whole-exome and Sanger sequencing studies, including paired tumor and control samples, have so far failed to reveal novel recurrent mutations but disclosed, instead, rare somatic or germline MPL or JAK2 variants [6] . Subsequent targeted deep sequencing studies have confirmed the presence of non-canonical MPL (i.e., other than MPL515L/K) or JAK2 (i.e., other than JAK2V617F) variants in some patients with triple-negative MPN [7–10] . The current study is focused on triplenegative PMF, assigned by institutional mutation screening methods with analytic sensitivity of 0.06% for JAK2V617F, 5% for CALR, and 10–20% for MPL.  \nThe current study was conducted under an institutional review board approved minimum risk protocol that allowed retrospective collection and analysis of data from patient records. Diagnostic criteria were according to the International Consensus Classification and confirmed by central review [11]; for the purposes of the current study, patients with accelerated phase PMF (i.e., PB or BM blasts ≥10%) were excluded. Cytogenetic results were reported according to the International System for Human Cytogenetic Nomenclature [12]; assignment as normal karyotype required examination of at least 10 metaphases and classification as“favorable” or “unfavorable” karyotype was according to previously published criteria [13] . Anemia was defined as “severe”(transfusion requiring or hemoglobin \u003C8 g/dL in women or \u003C9 g/ dL in men) or “moderate” (hemoglobin 8 to \u003C10 g/dL in women or 9 to \u003C11 g/dL in men) . Statistical analyses considered clinical and laboratory data collected at the time of initial diagnosis/referral. The Kaplan–Meier method was used to construct time-to-event curves, which were compared by the log-rank test. Multivariable logistic regression analysis was used to adjust for confounding variables. Cox regression analysis was applied to identify risk factors for overall (OS) and leukemia-free (LFS) survival. In survival analyses, patients were censored at the time of allogenic stem cell transplantation (ASCT) . Statistical analyses were conducted using  \nJMP Pro 17.0.0 software (SAS Institute, Cary, NC, USA) and Bluesky Statistics Software (Worldwide Headquarters, Chicago, IL, USA) .  \nA total of 92 (8.5%) patients with triple-negative PMF (median age 65 years; range 31–88; 53% males) were identified among 1085 molecularly-annotated patients with chronic phase PMF seen at the Mayo Clinic between 1980 and 2024 (chronic phase was defined according to formal criteria with bone marrow or peripheral blood blast percentage of \u003C10%) [5] . At presentation, median (range) values for hemoglobin were 9.4 g/dL [5–16], leukocyte count 6.8 × 109/L (1–146.6), absolute monocyte count (AMC) 0.4 × 109/","cbCairMCtMMWNzkv","https://ap.wps.com/l/cbCairMCtMMWNzkv","pdf",629948,"English","# Background\n## MPN-driver mutations and triple-negative definition\n# Study Methods\n## Review protocol and diagnostic criteria\n## Statistical analysis and endpoints\n# Patient Characteristics\n## Triple-negative PMF cohort vs JAK2-mutated comparator\n## Anemia, cytopenias, and mutation risk\n# Outcomes and Prognostic Factors\n## Mortality, leukemia transformation, and ASCT\n## Independent risk factors in survival models","[{\"question\":\"What does “triple-negative” PMF mean in this study?\",\"answer\":\"It refers to PMF cases in which routine mutation screening does not detect the canonical JAK2, CALR, or MPL driver mutations, operationally designated as “triple-negative MPN.” The study focuses on triple-negative PMF assigned by institutional mutation screening methods with specified analytic sensitivities.\"},{\"question\":\"How were patients selected and what disease stage was excluded?\",\"answer\":\"Patients were retrospectively collected under an institutional review board–approved protocol. Diagnostic criteria followed the International Consensus Classification, with central review confirmation, and accelerated-phase PMF with PB/BM blasts ≥10% was excluded.\"},{\"question\":\"Which statistical methods were used to evaluate prognosis and survival?\",\"answer\":\"Kaplan–Meier curves were built and compared using the log-rank test. Multivariable logistic regression adjusted for confounders, while Cox regression identified risk factors for overall survival (OS) and leukemia-free survival (LFS).\"},{\"question\":\"What independent risk factors were identified for overall survival in triple-negative PMF?\",\"answer\":\"In multivariable OS analysis, independent risk factors included age \\u003e65 years, hemoglobin \\u003c10 g/dL, leukocyte count \\u003e25 × 10^9/L, PB blasts ≥1%, and unfavorable karyotype.\"}]","Triple-negative primary myelofibrosis - a comparative analysis of phenotype, genotype, and outcome | PDF",1790696306,13]