Scholarlink

<p>Recent reports suggest a favorable prognosis for <i>PHF6</i> mutation (<i>PHF6</i><sup>MUT</sup>) in chronic myelomonocytic leukemia (CMML) and unfavorable in acute myeloid leukemia (AML). We accessed 176 consecutive patients with a spectrum of myeloid neoplasms with <i>PHF6</i><sup>MUT</sup>, including AML (<i>N</i> = 67), CMML (<i>N</i> = 49), myelodysplastic syndromes (MDS; <i>N</i> = 36), myeloproliferative neoplasms (MPN; <i>N</i> = 16), and MDS/MPN (<i>N</i> = 8). <i>PHF6</i> mutations were classified as nonsense (43%) or frameshift (30%) with the PHD2 domain being the most frequently (64%) affected region. Median follow-up was 25 months with 110 (63%) deaths and 44 allogenic transplants. Our top-line observations include (a) a distinctly superior overall survival (OS; 81 vs. 18 months; <i>p</i> &lt; 0.01) and blast transformation-free survival (BTFS; “not reached” vs. 44 months; <i>p</i> &lt; 0.01) in patients with CMML vs. those with other myeloid neoplasms, (ii) a higher than expected frequency of isolated loss of Y chromosome, in the setting of CMML (16% vs. expected 6%) and MDS (8% vs expected 2.5%), (iii) a significant association, in MDS, between <i>PHF6</i><sup>MUT</sup> variant allele fraction (VAF) &gt; 20% and inferior OS (HR 3.0, 95% CI 1.1–8.1, multivariate <i>p</i> = 0.02) as well as female gender and inferior BTFS (HR 26.8, 95% CI 1.9–368.3, multivariate <i>p</i> = 0.01), (iv) a relatively favorable median post-transplant survival of 46 months. Multivariable analysis also identified high-risk karyotype (HR 5.1, 95% CI 1.2–20.9, <i>p</i> = 0.02), and hemoglobin &lt;10 g/dL (HR 2.7, 95% CI 1.0–7.2, <i>p</i> = 0.04), as independent predictors of inferior OS in patients with MDS. The current study provides disease-specific information on genotype and prognosis of <i>PHF6</i>-mutated myeloid neoplasms.</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

Myeloid neoplasms with PHF6 mutations: context-dependent genomic and prognostic characterization in 176 informative cases

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月1日

查看全文
  • Saubia Fathima,
  • Ali Alsugair,
  • Rong He,
  • Abhishek A. Mangaonkar,
  • Kebede H. Begna,
  • Animesh Pardanani,
  • Cinthya J. Zepeda Mendoza,
  • Kaaren K. Reichard,
  • Naseema Gangat,
  • Ayalew Tefferi

摘要

Recent reports suggest a favorable prognosis for PHF6 mutation (PHF6MUT) in chronic myelomonocytic leukemia (CMML) and unfavorable in acute myeloid leukemia (AML). We accessed 176 consecutive patients with a spectrum of myeloid neoplasms with PHF6MUT, including AML (N = 67), CMML (N = 49), myelodysplastic syndromes (MDS; N = 36), myeloproliferative neoplasms (MPN; N = 16), and MDS/MPN (N = 8). PHF6 mutations were classified as nonsense (43%) or frameshift (30%) with the PHD2 domain being the most frequently (64%) affected region. Median follow-up was 25 months with 110 (63%) deaths and 44 allogenic transplants. Our top-line observations include (a) a distinctly superior overall survival (OS; 81 vs. 18 months; p < 0.01) and blast transformation-free survival (BTFS; “not reached” vs. 44 months; p < 0.01) in patients with CMML vs. those with other myeloid neoplasms, (ii) a higher than expected frequency of isolated loss of Y chromosome, in the setting of CMML (16% vs. expected 6%) and MDS (8% vs expected 2.5%), (iii) a significant association, in MDS, between PHF6MUT variant allele fraction (VAF) > 20% and inferior OS (HR 3.0, 95% CI 1.1–8.1, multivariate p = 0.02) as well as female gender and inferior BTFS (HR 26.8, 95% CI 1.9–368.3, multivariate p = 0.01), (iv) a relatively favorable median post-transplant survival of 46 months. Multivariable analysis also identified high-risk karyotype (HR 5.1, 95% CI 1.2–20.9, p = 0.02), and hemoglobin <10 g/dL (HR 2.7, 95% CI 1.0–7.2, p = 0.04), as independent predictors of inferior OS in patients with MDS. The current study provides disease-specific information on genotype and prognosis of PHF6-mutated myeloid neoplasms.