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 expressi on of TGF-beta 1 messenger RNA (TGF-beta mRNA) in myeloid cell lines a nd in patients with acute myeloid leukemia (AML) and chronic myeloid l eukemia (CML). In addition we determined the positivity for alpha 4 an d alpha 5 integrin molecules in those cells using specific monoclonal antibodies and flow cytometry. CML patients (N = 3) presented mean val ues 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 expre ssion of TGF-beta mRNA in K562 (derived from a patient with chronic my eloid leukemia) compared to the myeloblastic cell line HL60. The highe st TGF-beta mRNA levels were seen in the U937 lineage. CML leukemic ce lls (N = 3) showed high TGF-beta mRNA levels comparable to the levels expressed by K562 which was paralleled by high beta 1 integrin mRNA. A ML blast cells presented a variable degree of expression of TGF-beta m RNA when compared to HL60. One patient with acute megakaryoblastic leu kemia (FAB subtype M7), usually associated with myelofibrosis, present ed the highest TGF-beta mRNA levels. We conclude that studying TGF-bet a 1 and its mechanisms of action will help in understanding fibrosis i n leukemic patients, and perhaps to design treatments for such conditi ons.