Integrin receptors and TGF-beta expression in chronic myeloid leukemia cells.
To understand the relationship between transforming growth factor beta-1 (TGF-beta 1) and the integrin profile presented by chronic myeloid leukemia cells, we have studied, using Northern analysis, the expression of TGF-beta 1 messenger RNA (TGF-beta mRNA) in myeloid cell lines and in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition we determined the positivity for alpha 4 and alpha 5 integrin molecules in those cells using specific monoclonal antibodies and flow cytometry. CML patients (N = 3) presented mean values of alpha 4 and alpha 5 higher (alpha 4: 60 +/- 20%; alpha 5: 70 +/- 41%) than AML (N = 10) blast cells (alpha 4: 25 +/- 23%; alpha 5: 18 +/- 16%). Northern analysis revealed an almost four-fold higher expression of TGF-beta mRNA in K562 (derived from a patient with chronic myeloid leukemia) compared to the myeloblastic cell line HL60. The highest TGF-beta mRNA levels were seen in the U937 lineage. CML leukemic cells (N = 3) showed high TGF-beta mRNA levels comparable to the levels expressed by K562 which was paralleled by high beta 1 integrin mRNA. AML blast cells presented a variable degree of expression of TGF-beta mRNA when compared to HL60. One patient with acute megakaryoblastic leukemia (FAB subtype M7), usually associated with myelofibrosis, presented the highest TGF-beta mRNA levels. We conclude that studying TGF-beta 1 and its mechanisms of action will help in understanding fibrosis in leukemic patients, and perhaps to design treatments for such conditions.
Federico
M H
MH
Departamento de Radiologia, Faculdade de Medicina, Universidade de São Paulo, SP, Brasil.
Snitcovsky
I
I
Maistro
S
S
Katayama
M L
ML
Figueiredo
V L
VL
Brentani
M M
MM
D006801:Humans; D016023:Integrins / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016023:Integrins; D016212:Transforming Growth Factor beta