Heparanase expression in human leukemias is restricted to acute myeloid leukemias.
OBJECTIVE
Matrix metalloproteinases and an endo-beta-D-glucuronidase (heparanase) are enzymes that degrade the protein and carbohydrate constituents of basement membranes, thereby facilitating transendothelial migration of blood-borne cells. Heparanase activity was found to correlate with the metastatic potential of solid tumors. We evaluated heparanase expression, at the levels of gene and protein expression and activity in a variety of leukemias, and compared it with normal hematopoietic cells.


METHODS
Heparanase expression was evaluated in leukocytes isolated from peripheral blood of 71 patients with myeloid and lymphoid leukemias, or non-Hodgkin's lymphoma. Analysis was performed at two levels: heparanase RNA was determined by reverse transcriptase polymerase chain reaction, and heparanase protein was evaluated by immunocytochemistry and flow cytometry.


RESULTS
In eight peripheral blood samples from normal donors, heparanase RNA was detected, and protein was found within the cytoplasm of granulocytes. In mononuclear cells derived from various leukemias, heparanase RNA was expressed in 14 of 15 acute myeloid leukemia (AML) samples. In contrast, cells derived from all 33 chronic lymphoblastic leukemia, all 7 non-Hodgkin's lymphoma, 7 of 8 chronic myeloid leukemia, and 6 of 8 acute lymphoblastic leukemia patients showed no detectable expression of the heparanase RNA. Heparanase protein was detected primarily within the cytoplasm of AML cells, indicating that the enzyme is produced and stored within the cytoplasm of myeloid cells, with limited expression on the cell surface.


CONCLUSIONS
We propose that heparanase expression is associated with the myeloid lineage and may serve as an independent marker to support the identification of AMLs.
Bitan
Menachem
M
Department of Pediatrics, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
Polliack
Aaron
A
Zecchina
Gabriella
G
Nagler
Arnon
A
Friedmann
Yael
Y
Nadav
Liat
L
Deutsch
Varda
V
Pecker
Iris
I
Eldor
Amiram
A
Vlodavsky
Israel
I
Katz
Ben-Zion
BZ
D000208:Acute Disease; D019070:Cell Lineage / Q000235:genetics; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007945:Leukemia, Lymphoid / Q000201:enzymology / Q000235:genetics; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology / Q000235:genetics; D000099175:Heparanase
D005966:Glucuronidase; D000099175:Heparanase