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Histone Modification Patterns Using RPPA-Based Profiling Predict Outcome in Acute Myeloid Leukemia Patients.

Anneke D van Dijk1, Chenyue W Hu2, Eveline S J M de Bont1

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Proteomics
|March 6, 2018
PubMed
Summary

Histone-modifying proteins (HMP) show distinct expression patterns in acute myeloid leukemia (AML). These patterns significantly correlate with patient prognosis and survival outcomes in newly diagnosed AML.

Keywords:
Acute myeloid leukemiaHistone modificationRPPAReverse phase protein array

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Hematology

Background:

  • Posttranslational histone tail modifications are implicated in leukemogenesis.
  • These modifications represent potential therapeutic targets in cancer treatment.
  • The expression patterns of multiple histone-modifying proteins (HMP) in acute myeloid leukemia (AML) and their prognostic significance remain largely uninvestigated.

Purpose of the Study:

  • To globally analyze the expression levels and patterns of 20 HMP in newly diagnosed AML patients.
  • To investigate the correlation between HMP expression patterns and patient/disease characteristics, including survival and mutational status.
  • To identify distinct HMP expression clusters and their association with clinical outcomes.

Main Methods:

  • Reverse phase protein array (RPPA) was utilized to quantify 20 HMP in a cohort of 205 newly diagnosed AML patients.
  • Protein levels were correlated with clinical data, including survival and genetic mutations.
  • Hierarchical clustering was employed to identify HMP expression patterns (clusters).

Main Results:

  • Distinct clusters of HMP expression were identified, categorized as 'more on' (higher expression) or 'more off' (lower expression) relative to normal CD34+ cells.
  • The 'more on' HMP state was significantly associated with poorer patient outcomes and reduced survival.
  • FLT3-mutated AML cases were disproportionately represented in the 'more on' HMP expression state.
  • No significant correlation was observed between HMP states and DNA methylation-related mutations.

Conclusions:

  • HMP exhibit recurrent, distinct expression patterns in AML.
  • These HMP expression patterns serve as significant prognostic biomarkers for survival in newly diagnosed AML patients.
  • The findings highlight the potential of targeting HMP expression patterns for therapeutic strategies in AML.