Scholarlink

Abstract <p>Acute myeloid leukaemia with normal karyotype (AML-NK) is a cytogenetically cryptic yet heterogeneous clinical subgroup that lacks structural chromosomal abnormalities. Although classified as an intermediate-risk group, AML-NK exhibits variability in patient outcomes, underscoring the need for refined molecular stratification. In this study, high-throughput deep sequencing was performed on 51 AML-NK patients, with a comprehensive analysis of a Southeast Asian cohort to identify cryptic and novel fusion genes potentially implicated in disease pathogenesis and prognosis. Two pipelines (Arriba and STAR-fusion) were utilised in this study, which identified 68 findings involving 27 fusion genes, of which approximately 70% (<i>n</i> = 19/27) were novel. The majority (85%) were intrachromosomal fusion events, and 26% involved non-coding RNAs. The most recurrent and novel fusions were <i>LATS2::SAP18</i> (17.6%) and <i>HOXA3::HOXA9</i> (15.7%). In addition, known prognostic fusion genes, <i>KMT2A-</i>PTD<Emphasis Type="BoldItalic">,</Emphasis><i> NUP98::NSD1</i>, and <i>NPM1::MLF1</i>, were detected. The integration of these prognostic fusion genes into the ELN 2022 criteria reclassified 73% (<i>n</i> = 8/11) of intermediate-risk patients as poor-risk. Notably, the presence of <i>KMT2A-</i>PTD and/or <i>LATS2::SAP18</i> was associated with reduced overall survival (<i>p</i> = 0.039, Log-Rank), although this significance was not retained in multivariate analysis. This study’s findings revealed the complexity of the AML-NK transcriptome, highlighting the utility of RNA sequencing for prognostic risk assessment and therapeutic strategy development.</p> Key message <p><UnorderedList Mark="Bullet"> <ItemContent> <p>RNA-seq uncovered 27 fusion genes in AML-NK, 70% of which were novel.</p> </ItemContent> <ItemContent> <p>Recurrent LATS2::SAP18 and HOXA3::HOXA9 fusions were identified.</p> </ItemContent> <ItemContent> <p>Fusion-based ELN 2022 reclassified most intermediate-risk patients.</p> </ItemContent> <ItemContent> <p>RNA-seq enhances prognostic assessment in AML-NK. </p> </ItemContent> </UnorderedList></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

Identification of cryptic KMT2A-PTD and other novel fusion genes by transcriptome sequencing alters molecular risk stratification in AML-NK

  • 期刊论文

  • 发表日期：

    2026年1月22日

查看全文
  • Angeli Ambayya,
  • Rozaimi Razali,
  • Sarina Sulong,
  • Yee Yee Yap,
  • Veena Selvaratnam,
  • Jameela Sathar,
  • Rosline Hassan

摘要

Abstract

Acute myeloid leukaemia with normal karyotype (AML-NK) is a cytogenetically cryptic yet heterogeneous clinical subgroup that lacks structural chromosomal abnormalities. Although classified as an intermediate-risk group, AML-NK exhibits variability in patient outcomes, underscoring the need for refined molecular stratification. In this study, high-throughput deep sequencing was performed on 51 AML-NK patients, with a comprehensive analysis of a Southeast Asian cohort to identify cryptic and novel fusion genes potentially implicated in disease pathogenesis and prognosis. Two pipelines (Arriba and STAR-fusion) were utilised in this study, which identified 68 findings involving 27 fusion genes, of which approximately 70% (n = 19/27) were novel. The majority (85%) were intrachromosomal fusion events, and 26% involved non-coding RNAs. The most recurrent and novel fusions were LATS2::SAP18 (17.6%) and HOXA3::HOXA9 (15.7%). In addition, known prognostic fusion genes, KMT2A-PTD, NUP98::NSD1, and NPM1::MLF1, were detected. The integration of these prognostic fusion genes into the ELN 2022 criteria reclassified 73% (n = 8/11) of intermediate-risk patients as poor-risk. Notably, the presence of KMT2A-PTD and/or LATS2::SAP18 was associated with reduced overall survival (p = 0.039, Log-Rank), although this significance was not retained in multivariate analysis. This study’s findings revealed the complexity of the AML-NK transcriptome, highlighting the utility of RNA sequencing for prognostic risk assessment and therapeutic strategy development.

Key message

RNA-seq uncovered 27 fusion genes in AML-NK, 70% of which were novel.

Recurrent LATS2::SAP18 and HOXA3::HOXA9 fusions were identified.

Fusion-based ELN 2022 reclassified most intermediate-risk patients.

RNA-seq enhances prognostic assessment in AML-NK.