The expression of beta-tubulin gene in myelodysplastic syndrome evoluting to leukemia

Abstract

Based on our previous established cohort of myelodysplastic syndrome (MDS), we investigated the potential effect of beta-tubulin(TUBB) gene in the transformation of MDS into acute leukemia. From our nested case-control study cohort of MDS patients, we chose 11 paired transformed and non-transformed MDS patients. TUBB gene expression was tested by quantitative real-time PCR. TUBB-siRNA transfection was used to down-regulate TUBB gene expression in SKM-1 cell line. The function of TUBB gene in SKM-1 cell line was evaluated by cell proliferation, soft agar clone formation and electron microscope. TUBB gene expression in MDS patients in transformed group were significantly higher than that in control group (2.91±0.41 vs 0.90±0.23, P<0.01). After TUBB-siRNA transfection, A450/630nm of SKM-1 cells at 24 h, 48 h and 72 h were 0.299±0.045, 0.526±0.034 and 0.652±0.035, respectively, which were significantly decreased than those in negative-siRNA group(0.438±0.074, 0.858±0.064 and 0.974±0.044)(P<0.05). Soft agar clone formation in TUBB-siRNA group was (7.0±0.2)%, which was significantly reduced than that of negative-siRNA group (25.0±0.2)% (P<0.01). Electron microscope showed significant apoptotic signs in TUBB-siRNA group, including vacuoles in cytoplasm and karyorrhexis. Our results indicate that TUBB gene may play a role in the transformation of MDS into acute leukemia by affecting the proliferation of malignant clones.