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<p>Distinct bone marrow morphology is considered the primary basis for the&#xa0;diagnosis of <i>BCR::ABL1</i>-negative myeloproliferative neoplasms (MPNs). However, presence of a mutually exclusive classical driver mutation in <i>JAK2</i>, <i>CALR</i>, or <i>MPL</i> aids in diagnosing and determining the prognosis of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Few recent&#xa0;studies have&#xa0;reported presence of dual mutations in MPNs&#xa0;and&#xa0;double mutations in patients with PMF have been rarely described. We present two PMF patients with concurrent <i>MPL</i> and atypical <i>JAK2</i> mutations. Patient-P1 harbored <i>MPL</i>: p.W515L and <i>JAK2</i>: p.R867Q mutations and exhibited morphologic and clinical features consistent with PMF, overt fibrotic stage. Patient-P2 harbored <i>MPL</i>: p.W515L, <i>JAK2</i>: p.R683S, and <i>ASXL1</i>: p.G660Rfs*9 and&#xa0;presented with features consistent with PMF, early fibrotic phase. Both patients initially presented with isolated, increasing thrombocytosis, and never displayed&#xa0;the leukocytosis seen in many PMF cases. These cases highlight dynamic emergence of these co-mutations during MPN development and progression. They also illustrate the&#xa0;utility of broad molecular profiling in detecting canonical and atypical oncogenic mutations across genetically heterogeneous MPN that&#xa0;could assist in&#xa0;selecting treatment approaches&#xa0;to improve clinical outcomes.</p>

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Primary myelofibrosis with concurrent MPL and atypical JAK2 mutations

  • 期刊论文

  • 发表日期：

    2025年6月4日

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  • Subit Barua,
  • Cara Randall,
  • David Howell,
  • Gustavo Torres,
  • Ramakrishnan Sasi,
  • Sharathkumar Bhagavathi,
  • Peter L Perrotta

摘要

Distinct bone marrow morphology is considered the primary basis for the diagnosis of BCR::ABL1-negative myeloproliferative neoplasms (MPNs). However, presence of a mutually exclusive classical driver mutation in JAK2, CALR, or MPL aids in diagnosing and determining the prognosis of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Few recent studies have reported presence of dual mutations in MPNs and double mutations in patients with PMF have been rarely described. We present two PMF patients with concurrent MPL and atypical JAK2 mutations. Patient-P1 harbored MPL: p.W515L and JAK2: p.R867Q mutations and exhibited morphologic and clinical features consistent with PMF, overt fibrotic stage. Patient-P2 harbored MPL: p.W515L, JAK2: p.R683S, and ASXL1: p.G660Rfs*9 and presented with features consistent with PMF, early fibrotic phase. Both patients initially presented with isolated, increasing thrombocytosis, and never displayed the leukocytosis seen in many PMF cases. These cases highlight dynamic emergence of these co-mutations during MPN development and progression. They also illustrate the utility of broad molecular profiling in detecting canonical and atypical oncogenic mutations across genetically heterogeneous MPN that could assist in selecting treatment approaches to improve clinical outcomes.