The differential expression pattern of the BMI-1, SALL4 and ABCA3 genes in myeloid leukemia

Abstract

Background and methodsIn order to characterize the expression pattern of SALL4, BMI-1 and ABCA3 genes in patients with myeloid leukemia and those who achieved complete remission (CR) after chemotherapy. Real-time PCR was used to determine the expression level of these genes in peripheral blood mononuclear cells from 24 patients with AML, eight patients with AML-CR, 13 patients with CML in the chronic phase (CML-CP), 12 patients with CML in blast crisis (CML-BC), 13 patients with CML-CR and 11 healthy individuals (HI).ResultsOverexpression of the BMI-1 gene was found in the AML, CML-CP and CML-BC groups as compared with HI group, while the BMI-1 expression level was lower in patients who achieved CR. In contrast, significantly increased SALL4 expression was only found in AML group, additionally, SALL4 expression was lower in the CML-CP and CML-CR groups compared with the HI group, while the SALL4 expression level in the CML-BC group was higher and significantly greater than that in the CML-CP and CML-CR groups. Moreover, a positive correlation between the expression of SALL4 and BMI-1 genes was found in samples from most groups. There was no significant difference of ABCA3 expression level in AML and CML-BC group in comparison with HI group. Interestingly, the ABCA3 expression level was significantly decreased in the CML-CP, AML-CR and CML-CR in comparison with the HI group. Moreover, the ABCA3 expression level in all of the CR groups was lower than that in their corresponding groups.ConclusionsThese results describe the altered SALL4, ABCA3 and BMI-1 expression pattern in different phases of myeloid leukemia, which may relate to the development and progression to different diseases. SALL4 expression was strongly correlated with BMI-1 in most of the myeloid leukemia patient groups, providing a potential link between SALL4 and BMI-1 in leukemogenesis.

Sall4 overexpression blocks murine hematopoiesis in a dose-dependent manner

“…Our data, using normal bone marrow rather than cell lines or reporter systems, shows that a high degree of Sall4 overexpression suppresses Bmi1, which contradicts the reported positive correlation of Sall4 on Bmi1 expression in models where Sall4 was associated with enhanced self-renewal [6, 22, 29]. Bmi1 is a member of Polycomb Repressive Complex 1, and has been shown to be a critical regulator of hematopoiesis and leukemopoiesis [30, 39, 40].…”

“…Interestingly, these results directly contradict the reported positive correlation between Sall4 and Bmi1 in hematopoiesis [6, 22, 29]. Pten was modestly decreased by both Sall4a and Sall4b, in keeping with previous reports that also showed modest repression of Pten by Sall4 [23].…”

SALL4, the missing link between stem cells, development and cancer

“…Consistent with this observation, aberrant hypomethylation of SALL4 gene in MDS patients has also been reported 37,97 . Increased SALL4 expression was detected in patient samples from blastic stage of chronic myeloid leukemia (CML), compared to the chronic phase, CML patients who have achieved complete remission (CR) after chemotherapy groups 90 , or those who have tyrosine kinase inhibitor (TKI) resistance 98 . SALL4 is constitutively expressed in most human primary acute myeloid leukemia (AML) and myeloid leukemia cell lines 65 .…”

“…SALL4 can also regulate other ESC genes such as Nanog, Pou5f1 , and SOX2 . In addition, in normal human hematopoietic and leukemic cells, SALL4 can up-regulate the expression of BMI-1 95,98,140 . HOXA9 22,89 , and down-regulate PTEN expression 49 .…”

Deregulation of Bmi-1 is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma

“…Bmi-1(B-cell specific Moloney murine leukemia virus insertion site 1),a transcriptional repressor of polycomb group of transcription factors, had been found to involve in self renewal of hematopoietic [5], neuronal [6] and mammary [7] stem cells, and has been implicated in the tumorigenesis of various malignancies, including leukemia [8], lymphomas [9], non-small cell lung cancer [10], breast cancer [11] and nasopharyngeal carcinoma [12]. Moreover, Bmi-1 was also found to play a key role in tumor metastasis [13].…”