Abstract

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia (7.15 ± 2.18) and solid tumor groups (7.11 ± 1.47), but both were higher than in the MDS group (5.12 ± 1.29) and benign blood diseases group (3.08 ± 1.08). Taking 7.15%, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group (MNF ≥ 7.15%) and low MNF group (MNF<7.15%). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

Highlights

  • Micronucleus (MN) is a form of chromosome aberration in karyocyte

  • Whole blood (0.2 ml-1ml according to blood routine test) incubated for 72 hours at 37°C in 5 mL of culture medium supplemented with 80% RPMI1640, 10% fetal calf serum, 10% phytohemagglutinin, 100 U/ mL penicillin, and 100 μg/mL streptomycin

  • Scoring of the micronucleus with criteria set by Countryman, et al (Countryman and Heddle, 1976), For each case,1,000 lymphocytes were analyzed

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Summary

Introduction

Micronucleus (MN) is a form of chromosome aberration in karyocyte. Some fragments stay in the cytoplasm of daughter cells after mitosis. They form one or more secondary nucleus, and known as micronucleus. The micronucleus embeds in cytoplasm,the diameter is 1/20 to 1/3 of the nucleus. The frequency of a micronucleus occurrence has positive correlation with chromosome aberration (Kuramoto et al, 2002; Smith et al, 2003; Fenech, 2006; Hamza et al, 2009; JuchimiukKwasniewska et al, 2011). This can reflect chromosome damage at a certain degree. Much theoretical evidence has accumulated supporting the causal role of MN induction in cancer development

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