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


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


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.
Eisenkraft
Arik
A
Department of Pediatrics, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel. aizenkra@017.net.il
Keidan
Ilan
I
Bielorai
Bela
B
Keller
Nathan
N
Toren
Amos
A
Paret
Gideon
G
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000453:epidemiology; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000473:pathology
D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2