Biological and clinical relevance of matrix metalloproteinases 2 and 9 in acute myeloid leukaemias and myelodysplastic syndromes.
We analysed by immunocytochemistry metalloproteinase (MMP)-2 and MMP-9 expression in bone marrow cells from 54 acute myeloid leukaemia (AML) patients, 153 myelodysplastic syndrome (MDS) patients, and 52 non-haemopathic subjects, in order to evaluate whether MMP expression abnormalities were associated with relevant laboratory or clinical findings. In normal samples MMP-2 was detected in rare myeloid cells, MMP-9 in most maturing myeloid cells. In MDS MMP-2 myeloid levels were higher than in controls (P < 0.0001); MMP-2 and MMP-9 were often co-expressed. Also many erythroblasts expressed MMP-2. There was a positive correlation between MMP-2 erythroblast expression and erythroid dysplasia (P = 0.002) and an inverse correlation between MMP-2 or MMP-9 myeloid expression and blast cell percentage (P = 0.05 and P = 0.04 respectively). High MMP levels in myeloid cells were associated with longer overall survival (P = 0.03) and evolution-free survival (P = 0.04). In AML MMP-2 levels were lower than in MDS (P < 0.0001) and MMP-9 levels lower than in MDS and controls (P < 0.0001). MMP levels did not predict response to therapy. The release of active MMPs was detected by colorimetric analysis in cell cultures from representative MDS and AML cases. In conclusion, we have demonstrated an abnormal MMP expression in AML as well as in MDS. The production and release of these enzymes may influence haematopoietic cell behaviour. In MDS, the detection of MMP deregulated expression may be important also from the clinical point of view: it may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments.
Travaglino
Erica
E
Department of Internal Medicine, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
Benatti
Chiara
C
Malcovati
Luca
L
Della Porta
Matteo Giovanni
MG
Gallì
Anna
A
Bonetti
Elisa
E
Rosti
Vittorio
V
Cazzola
Mario
M
Invernizzi
Rosangela
R
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001853:Bone Marrow / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004900:Erythroblasts / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000201:enzymology* / Q000473:pathology; D022423:Myeloid Cells / Q000201:enzymology / Q000473:pathology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D014407:Tumor Cells, Cultured
C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9