{
  "abstract": "Recent prospective studies demonstrated that reductions in JAK2 V617F variant allele frequency (VAF) correlate with clinical benefit in essential thrombocythemia (ET) and polycythemia vera (PV). 1,2 However, the impact of CALR VAF dynamics with therapy on clinical outcomes remains relatively unknown. Pegylated interferon-alpha (IFN) has been shown to variably reduce CALR VAF, but changes with treatments such as hydroxycarbamide (HC), anagrelide (ANA), and ruxolitinib (RUX), a JAK inhibitor, are less well described. 3 Newer mutation-targeted therapies are demonstrating early significant reductions in VAFs, which may serve as a surrogate marker of disease modification. 4 We therefore sought to evaluate dynamics of driver mutation VAF in myeloproliferative neoplasm (MPN) patients treated with cytoreductive therapies and correlate these with clinical outcomes. Sequential cases were collated from eight international centers including the prospective MAJIC-ET study. 5 Although MAJIC-ET has been reported, inclusion enabled greater power for time-dependent outcomes. A comparator cohort of JAK2 V617F -mutated patients was included; the MAJIC-PV cohort was excluded due to substantially higher baseline VAF precluding meaningful comparison. CALR VAF was quantified using next-generation sequencing (NGS), fragment analysis, or droplet digital polymerase chain reaction (ddPCR). JAK2 V617F VAF was quantified using quantitative PCR or NGS. Serial VAF measurements within each patient were performed using the same analytical platform at the same center throughout follow-up. Molecular response (MR), comprising complete (CMR) and partial (PMR) response as defined per IWG-MRT/ELN 2013 criteria, plus an exploratory PMR20 category, is detailed in Supporting Information S2: Supplementary Methods. 6-8 Overall, 347 patients with CALR (n = 190) and JAK2 V617F (n = 157) mutations with VAF measurements at two timepoints at least 6 months apart were included (Table 1). ET was the most prevalent diagnosis (n = 235, 67.7%), followed by primary and secondary myelofibrosis (MF; n = 73, 21.1%), prefibrotic myelofibrosis (n = 17, 4.9%), PV (n = 15, 4.3%), MPN-unclassified (n = 6, 1.7%), and blast-phase MPN (n = 1, 0.3%). Treatment was defined as the predominant cytoreductive agent active between the first and second VAF measurements (Supporting Information S2: Supplementary Methods). Treatments included IFN (n = 132, 38.0%), RUX (n = 70, 20.2%), ANA (n = 29, 8.4%), HC (n = 88, 25.4%), and other therapies (n = 28, 8.0%) (Table 1). Median VAF measurement interval was 54 months (range HemaSphere.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "Zi Yun Ng"
    },
    {
      "name": "Laurane Cottin"
    },
    {
      "name": "Marine Demoy"
    },
    {
      "name": "Damien Luque Paz"
    },
    {
      "name": "Corentin Orvain"
    },
    {
      "name": "Wayne‐corentin Lambert"
    },
    {
      "name": "Jean‐christophe Ianotto"
    },
    {
      "name": "Eric Lippert"
    },
    {
      "name": "David M Ross"
    },
    {
      "name": "Diana Iarossi"
    },
    {
      "name": "Alesia Khan"
    },
    {
      "name": "Daniel Lock"
    },
    {
      "name": "Catherine Truong"
    },
    {
      "name": "Kamel Laribi"
    },
    {
      "name": "Yun Fan Yang"
    },
    {
      "name": "Laura Li Gagnon"
    },
    {
      "name": "Valerie Ugo"
    },
    {
      "name": "Claire N Harrison"
    },
    {
      "name": "Jennifer O'Sullivan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0w2ya20bbnzsp.bib",
  "cited_by": 0,
  "doi": "10.1002/hem3.70460",
  "fulltext_url": null,
  "id": "0w2ya20bbnzsp",
  "issns": [
    "2572-9241"
  ],
  "landing_url": "https://hal.science/hal-05753482v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2716|Myeloproliferative Neoplasms: Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7204794114",
  "pdf_url": "https://hal.science/hal-05753482/document",
  "pmcid": null,
  "pmid": "42677099",
  "published": "2026-08-31",
  "publisher": "Lippincott, Williams & Wilkins",
  "ris": "https://research.draconitic.com/paper/0w2ya20bbnzsp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:36Z",
      "native_id": "hal-05753482",
      "source": "hal",
      "url": "https://hal.science/hal-05753482v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Myeloproliferative Neoplasms: Diagnosis and Treatment",
      "subfield": "human-genetics"
    }
  ],
  "title": "Allele burden expansion in JAK2 V617F and CALR ‐mutated myeloproliferative neoplasms predicts disease progression and is associated with anagrelide treatment",
  "title_text": "Allele burden expansion in JAK2 V617F and CALR ‐mutated myeloproliferative neoplasms predicts disease progression and is associated with anagrelide treatment",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:36Z",
  "url": "https://research.draconitic.com/paper/0w2ya20bbnzsp",
  "venue": "HemaSphere",
  "versions": []
}