CD34 expression predicts an adverse outcome in patients with NPM1-positive acute myeloid leukemia

Hum Pathol. 2013 Oct;44(10):2038-46. doi: 10.1016/j.humpath.2013.03.007. Epub 2013 May 21.

Abstract

Patients with acute myeloid leukemia (AML) harboring an NPM1 mutation exhibit a heterogeneous clinical outcome. Recent studies have shown that the absence of FLT3 internal tandem duplication (FLT3-ITD) mutation confers a favorable prognosis in NPM1-positive AML. However, the prognostic impact of immunophenotypes in this subgroup remains unclear. In this study, FLT3 mutation status and immunophenotypic profile of 85 NPM1-positive patients with de novo AML were retrospectively analyzed and correlated with their clinical features and survival outcomes. Univariate analysis detected 5 markers with prognostic relevance: older age (≥60 years), high white blood cell (WBC) count (>30 × 10(9)/L), FLT3-ITD, CD7, and CD34 expression. Multivariate analysis showed that high WBC count was the only independent predictor of a lower complete remission rate (P = .019). Older age (P = .035), high WBC count (P = .008), FLT3-ITD (P = .012), and CD34 expression (P = .006) were independent predictors of a shorter event-free survival (EFS). High WBC count (P = .014), FLT3-ITD (P = .005), and CD34 expression (P = .047) were independent predictors of a shorter overall survival (OS). Furthermore, based on FLT3-ITD status in NPM1 mutation-positive patients, we showed that both high WBC and CD34 expression conferred a poor EFS (P = .010 and P = .016, respectively) and OS (P = .032 and P = .001, respectively) in the FLT3-ITD-negative group, whereas high WBC predicted a poor EFS (P = .016) and OS (P = .027) in the FLT3-ITD-positive group. Our results confirm the prognostic value of assessing FLT3-ITD mutations in NPM1-positive AML and identify the adverse prognostic impact of high WBC and CD34 expression in this subgroup of AML.

Keywords: Acute myeloid leukemia; FLT3-ITD; Immunophenotyping; NPM1; Prognosis.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Bone Marrow Cells
  • Canada / epidemiology
  • DNA Mutational Analysis
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Karyotyping
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / mortality
  • Leukocyte Count
  • Leukocytosis / pathology
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Prognosis
  • Retrospective Studies
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antigens, CD34
  • Biomarkers, Tumor
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3