MCP-1 in the cerebrospinal fluid of children with acute lymphoblastic leukemia

Leuk Res. 2006 Oct;30(10):1259-61. doi: 10.1016/j.leukres.2006.01.017. Epub 2006 Mar 3.

Abstract

Background: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokines. MCP-1 has been previously shown to have a major role in the migration of monocytes towards human leukemic cells, yet it cannot increase cytotoxic effects of monocytes on human leukemic cells.

Aim: To determine levels of MCP-1 in the CSF of children during various stages of acute lymphoblastic leukemia (ALL).

Patients and methods: A 19 children with ALL and without known CNS involvement were enrolled in the study. CSF samples were aliquoted at different stages of therapy (diagnosis, induction, and maintenance) and were frozen at -70 degrees C until use. MCP-1 was measured with a sandwich enzyme-linked immunoabsorbent assay.

Results: Mean MCP-1 levels in the CSF were 1762.38 pg/ml (range 522-5000 pg/ml). In children without CNS involvement at diagnosis, CSF MCP1 levels did not change over time and remained within this range throughout the diagnosis and treatment stages. CNS involvement was associated with an increased MCP-1 level following chemotherapy, in patients with CNS involvement from 840 to 3990 pg/ml (P<0.0001), and in patients without CNS involvement from 1134 to 1943 pg/ml (P-value of 0.0322). White blood cells found in the CSF at diagnosis have vanished after induction.

Conclusions: CNS involvement in ALL is associated with significantly higher levels of MCP1 during therapy. This significant rise in MCP-1 levels might be one of the mechanisms involved in the regulation of CNS leukemia. Since chemokines target specific leukocyte subsets, inhibition of a single Chemokine ligand or receptor may have a circumscribed effect, endowing the inhibitor with a limited side effect profile. Chemokines should be considered as possible targets for therapeutic intervention.

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / cerebrospinal fluid
  • Central Nervous System Diseases / cerebrospinal fluid
  • Central Nervous System Diseases / epidemiology
  • Chemokine CCL2 / cerebrospinal fluid*
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Neoplasm Staging
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / cerebrospinal fluid*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

Substances

  • Biomarkers, Tumor
  • CCL2 protein, human
  • Chemokine CCL2