Change of SALL4 and BMI-1 Expression Levels in Hematologic Malignancies

Abstract 4642

The polycomb gene BMI-1 plays an essential role in regulating adult, self-renewing hematopoietic stem cells (HSCs). The SALL4 zinc-finger transcription factor, which is a member of the SALL gene family, may regulate BMI-1 gene expression by dose-dependent. BMI-1 and SALL4 are putative oncogenes that modulate stem cell pluripotency and play a role in leukemogenesis. Overexpression of both genes was found in acute leukemia and so on. In the present study, we analyzed the expression and its correlation of SALL4 and BMI-1 in Chinese patients with hematologic malignancies. Real-time PCR with SYBR Green±technique was used for detecting the expression level in peripheral blood mononuclear cells from 11 patients with de novo acute myeloid leukemia (AML), 10 patients with AML in complete remission (CR), 13 patients with de novo chronic myelocytic leukemia in chronic phase (CML), 13 patients with CML-CR, 22 patients with de novo acute lymphoblastic leukemia (ALL) (including T-cell acute lymphoblastic leukemia (T-ALL) 12 cases, B-cell acute lymphoblastic leukemia (B-ALL) 10 cases),10 patients with multiple myeloma (MM) and 12 healthy individuals. β2-microglobulin gene (β2M) was used as an endogenous reference. Relative changes in SALL4 and BMI-1 expression levels were used by the 2^{− ¢Ct}×100% method. The results showed that the expression levels of SALL4 in B-ALL (2.573±2.503%), T-ALL (1.738±1.077%), and AML (3.049±4.712%) groups were significant higher than those in the healthy group (0.847±1.326%) (P<0.05, P<0.01, P<0.05). However, in AML-CR (0.107±0.157%) and CML-CR (0.031±0.018%) groups, the expression levels of SALL4 were lower than the control (P<0.01, P<0.01). The change of the SALL4 gene expression level also could be found between AML and AML-CR groups (P<0.01), CML (0.258±0.31%) and CML-CR groups (P<0.01). And by comparing with the healthy group (0.098±0.172%), the expression level of BMI-1 were significant higher in B-ALL (0.518±0.837%), T-ALL (0.335±0.267%), AML (0.667±0.959%), CML (0.701±1.081%) and MM (0.32±0.337%) groups (P<0.05, P<0.01, P<0.05, P<0.05, P<0.05), whereas lower only in CML-CR (0.005±0.004%) group (P<0.01). BMI-1 also had significant difference between AML and AML-CR groups (0.127±0.166%) (P<0.05), CML and CML-CR groups (P<0.01). Moreover, the expression of BMI-1 was positively correlated with that of SALL4 in healthy group (r=0.687, P<0.05), T-ALL (r=0.86, P<0.01), AML (r=0.735, P<0.05), AML-CR (r=0.745, P<0.05), CML (r=0.742, P<0.01) and CML-CR (r=0.534, P<0.05). These results indicated that overexpression of SALL4 and BMI-1 is a common feature in most types of leukemia and may relate to leukemogenesis, which is significant downregulated during the disease in complete remission. Further work is needed to analyze more samples, follow up on the outcome of patients and summarize the significance of change of expression pattern of both genes.