4.8 Article

Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios

Journal

NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31489-9

Keywords

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Funding

  1. Guangdong Basic and Applied Basic Research Foundation [2021A1515011809]
  2. Guangzhou Science and Technology Program Key Projects [201803010032]
  3. Bethune Medical Scientific Research Fund Project [SCE111DS]
  4. Sun Yat-sen Sailing Scientific Research Project [YXQH202205]

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This study explores the relationship between FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identifies an optimal threshold value, highlighting the importance of individualized treatment for pediatric AML.
Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML. Activating FLT3 mutations are the most common mutations in AML. Here, the authors explore the relationship between the FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identify an optimal threshold to stratify patients.

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