High expression of Midkine (MK) indicates poor prognosis in childhood acute lymphoblastic leukemia

Hematology. 2016 Mar;21(2):69-77. doi: 10.1179/1607845415Y.0000000050. Epub 2015 Sep 9.

Abstract

Objectives: Midkine (MK) expression has been reported to be correlated with the poor prognosis of patients with various tumors. However, there are no data available about the prognostic value of MK expression in childhood acute lymphoblastic leukemia (ALL).

Methods: In this study, MK mRNA expression was determined by real-time polymerase chain reaction in 120 childhood ALL and 30 healthy volunteers. Patients were dichotomized at the median value and divided into two groups: MK(low) group and MK(high) group.

Results: MK(high) patients had higher white blood cell counts, higher peripheral blood blasts percentages, and higher minimal residual disease levels than MK(low) patients. Moreover, the MK gene was expressed significantly higher in patients with relapsed ALL than in patients who maintained complete remission or at diagnosis. MK(high) patients harbored inferior relapse-free survival (RFS, P = 0.047) and overall survival (OS, P = 0.022) than MK(low) patients, and high expression of MK was found to be independently predictive of inferior OS (P = 0.032) but not RFS (P = 0.077) in the overall cohort.

Conclusion and discussion: MK high expression is an independent adverse prognostic factor in childhood ALL. Its level may be incorporated into an improved risk classification system for ALL and suggest the need of alternative regimens.

Keywords: Acute lymphoblastic leukemia; Childhood; Midkine; Prognosis.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Blast Crisis / blood*
  • Blast Crisis / mortality*
  • Blast Crisis / therapy
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Infant
  • Leukocyte Count
  • Male
  • Midkine
  • Neoplasm Proteins / biosynthesis*
  • Nerve Growth Factors / biosynthesis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Survival Rate

Substances

  • MDK protein, human
  • Neoplasm Proteins
  • Nerve Growth Factors
  • Midkine