Positive Health Online

Abstract

TAN and COLLEAGUES,      1 Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China; 2 Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou 510230, China;           3 Department of Hematology, Huizhou Municipal Central Hospital, Huizhou 516001, China; 4 Clinical Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China study at the molecular level the mechanism of myeloid differentiation blockage in myeloid leukaemia.

Background

High-mobility group AT-hook 2 (HMGA2) may serve as an architectural transcription factor, and it can regulate a range of normal biological processes including proliferation and differentiation. Upregulation of HMGA2 expression is correlated to the undifferentiated phenotype of immature leukaemic cells. However, the underlying mechanism of HMGA2-dependent myeloid differentiation blockage in leukaemia is unknown.

Methodology

To reveal the role and mechanism of HMGA2 in differentiation arrest of myeloid leukaemia cells, the quantitative expression of HMGA2 and homeobox A9 (HOXA9) was analysed by real-time PCR (qRT-PCR). The regulatory function of HMGA2 in blockage of differentiation in human myeloid leukaemia was investigated through in vitro assays (XTT assay, May-Grünwald-Giemsa, flow cytometry analysis and western blot).

Results

We found that the expression of HMGA2 and HOXA9 was reduced during the process of granulo-monocytic maturation of acute myeloid leukaemia (AML) cells, knockdown of HMGA2 promotes terminal (granulocytic and monocytic) differentiation of myeloid leukaemia primary blasts and cell lines, and HOXA9 was significantly downregulated in leukaemic cells with knockdown of HMGA2. Downregulation of HOXA9 in myeloid leukaemia cells led to increased differentiation capacity in vitro.

Conclusion

Our data suggest that increased expression of HMGA2 represents a possible new mechanism of myeloid differentiation blockage of leukaemia. Aberrant expression of HMGA2 may enhance HOXA9-dependent leukaemogenesis and myeloid leukaemia phenotype. Disturbance of the HMGA2-HOXA9 pathway is probably a therapeutic strategy in myeloid leukaemia.

References

Li Tan  1   2 , Hongfa Xu  1 , Guoshu Chen  3 , Xiaoping Wei  4 , Baodan Yu  4 , Jingmei Ye  1 , Lihua Xu  1   2 , Huo Tan  1. Silencing of HMGA2 reverses retardance of cell differentiation in human myeloid leukaemia Br J Cancer;118(3):405-415. doi: 10.1038/bjc.2017.403. Epub 2018 Jan 2. Feb 6 2018.

Comment

The above research demonstrated that aberrant expression of High-mobility group AT-hook 2 (HMGA2) may enhance homeobox A9  HOXA9-dependent leukaemogenesis and myeloid leukaemia phenotype. Disturbance of the HMGA2-HOXA9 pathway is probably a therapeutic strategy in myeloid leukaemia.