Scholarlink

<p><i>NPM1</i>-mutated (<i>NPM1</i>c) acute myeloid leukemia (AML) has traditionally been considered a genetically defined entity associated with a favorable prognosis. However, growing evidence indicates that <i>NPM1</i>c AML comprises biologically and clinically heterogeneous disease states, in which <i>NPM1</i>c acts less as an autonomous prognostic determinant and more as a context-dependent organizer of leukemic architecture. Integrative transcriptomic and epigenomic studies have identified reproducible stemness-linked programs, including primitive and committed subtypes, the primitive phenotype being associated with inferior survival and increased relapse risk even within conventionally favorable groups. Single-cell and clonal architecture analyses further support a hierarchical model whereby early epigenetic lesions shape differentiation trajectories and constrain the phenotypic output of subsequent <i>NPM1</i> and signaling mutations. In parallel, large-scale sequencing studies reveal non-random co-mutational patterns and variant allele frequency hierarchies, where epigenetic mutations frequently precede <i>NPM1</i>c and signaling alterations emerge later during leukemic evolution. Collectively, these findings support risk-stratification frameworks that integrate the leukemic cell state, transcriptional identity, and mutational hierarchy, moving from mutation-centric toward architecture-informed models for prognosis and therapeutic decision-making in <i>NPM1</i>c AML.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Leukemic architecture as a framework for risk stratification in NPM1-mutated acute myeloid leukemia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月8日

查看全文
  • Francesco Tarantini,
  • Luisa Anelli,
  • Antonella Zagaria,
  • Cosimo Cumbo,
  • Nicoletta Coccaro,
  • Angela Minervini,
  • Giuseppina Tota,
  • Maria Rosa Conserva,
  • Immacolata Redavid,
  • Crescenzio Francesco Minervini,
  • Elisa Parciante,
  • Giorgina Specchia,
  • Pellegrino Musto,
  • Francesco Albano

摘要

NPM1-mutated (NPM1c) acute myeloid leukemia (AML) has traditionally been considered a genetically defined entity associated with a favorable prognosis. However, growing evidence indicates that NPM1c AML comprises biologically and clinically heterogeneous disease states, in which NPM1c acts less as an autonomous prognostic determinant and more as a context-dependent organizer of leukemic architecture. Integrative transcriptomic and epigenomic studies have identified reproducible stemness-linked programs, including primitive and committed subtypes, the primitive phenotype being associated with inferior survival and increased relapse risk even within conventionally favorable groups. Single-cell and clonal architecture analyses further support a hierarchical model whereby early epigenetic lesions shape differentiation trajectories and constrain the phenotypic output of subsequent NPM1 and signaling mutations. In parallel, large-scale sequencing studies reveal non-random co-mutational patterns and variant allele frequency hierarchies, where epigenetic mutations frequently precede NPM1c and signaling alterations emerge later during leukemic evolution. Collectively, these findings support risk-stratification frameworks that integrate the leukemic cell state, transcriptional identity, and mutational hierarchy, moving from mutation-centric toward architecture-informed models for prognosis and therapeutic decision-making in NPM1c AML.