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

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.