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MCP-1 in the cerebrospinal fluid of children with acute lymphoblastic leukemia
Arik Eisenkraft1, Ilan Keidan, Bela Bielorai
1Department of Pediatrics, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel. aizenkra@017.net.il
Insights
Monocyte chemoattractant protein-1 (MCP-1) levels in cerebrospinal fluid (CSF) are elevated in children with acute lymphoblastic leukemia (ALL) when central nervous system (CNS) involvement occurs. This suggests MCP-1 may play a role in CNS leukemia regulation.
Area of Science:
- Pediatric Oncology
- Immunology
- Neuroscience
Background:
- Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine crucial for monocyte migration.
- MCP-1 facilitates monocyte recruitment to leukemic cells but does not enhance monocyte cytotoxicity.
- Understanding MCP-1's role in CNS leukemia is vital for therapeutic strategies.
Purpose of the Study:
- To quantify MCP-1 levels in the cerebrospinal fluid (CSF) of pediatric patients with acute lymphoblastic leukemia (ALL).
- To investigate MCP-1 level variations across different stages of ALL therapy.
- To correlate MCP-1 levels with the presence or absence of central nervous system (CNS) involvement.
Main Methods:
- A cohort of 19 children diagnosed with ALL was studied.
- CSF samples were collected at diagnosis, induction, and maintenance therapy phases.
- MCP-1 concentrations were determined using a sandwich enzyme-linked immunoabsorbent assay (ELISA).
Main Results:
- Mean MCP-1 levels in CSF were 1762.38 pg/ml.
- In patients without CNS involvement, MCP-1 levels remained stable throughout therapy.
- CNS involvement correlated with a significant increase in MCP-1 levels post-chemotherapy (P<0.0001).
Conclusions:
- Elevated CSF MCP-1 levels are significantly associated with CNS involvement in pediatric ALL during therapy.
- Increased MCP-1 may contribute to the pathogenesis of CNS leukemia.
- Chemokines like MCP-1 represent potential therapeutic targets for CNS leukemia with a favorable side effect profile.
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.
