Expression of Apoptosis-Controlling Proteins in Acute Leukemia Cells

Abstract

The expression of Bcl-2 family proteins (Bcl-2, Bcl-X, Bcl-X_L, Bcl-X_s, BAX, BAD, MCL-1) and of Interleukin-1 converting enzymc (ICE)-related proteins (ICE, CPP32, ICH- 1) was analyzed in acute leukemia cells by flow cytometry. Most proteins studied were detectable in cell lines such as KG la, HL60, K562 (myeloblastic), REH, RAJI and MOLT4 (lymphoblas-tic) and VAL (B-cell lymphoma). However, BCL-X, and BAK were weakly expressed in K562, as were Bcl-X, BAD and BAK in the VAL line. In acute myeloid leukemia (66 cases studied), the proteins were expressed in most cases in a high percentage of cells, especially BAX and CPP32, without correlation with hematological characteristics. However, Bcl-2 was expressed in a higher percentage of cells in FAB MI and M5 cases, and in CD34-positive cases, whereas Bcl-X_s, was more frequently expressed in M3 cases. No differences were observed regarding fluorescence intensity. Higher percentages of Bcl-2-positive cells were associated with low remission rate, while expression of Bcl-X_s, was predictive of high remission rate. In acute lymphoblastic leukemia (36 cases), all proteins studied were expressed in a majority of cases. Bcl-X_s, was more frequently detected in T-cell type, and was also associated with a higher remission rate. These results suggest that apoptosis-controlling proteins may have a role in the pathogenesis and response to therapy of acute leukemia.

Key Words:

• apoptosis
• acute leukemia
• caspases
• Bcl-2 family