Up-regulated MSI2 is associated with more aggressive chronic myeloid leukemia

Abstract

A better understanding of events triggering chronic myeloid leukemia progression is critical for optimized clinical management of chronic myeloid leukemia (CML). We sought to validate that increased expression of Musashi 2 (MSI2), a post-transcription regulator, is associated with progression and prognosis. Screening of 152 patients with CML showed that MSI2 was significantly decreased among patients with CML in chronic phase (CP) at diagnosis (p < 0.0001), but found no significant difference between the normal control group and treated patients with CML in CP. Moreover MSI2 was significantly increased (p < 0.0001) in patients with advance disease (AD) CML. Furthermore, our human hematopoietic cell line data imply that MSI2 and BCR-ABL1 mRNA expression are correlated. However, these data cast a doubt on earlier reports that MSI2 effects HES1 expression via NUMB–NOTCH signaling.

Keywords::

• Prognosis
• transformation
• MSI2
• leukemia
• stem cell

Acknowledgements

The study was supported by a research grant from Berliner Krebsgesellschaft e.V. (KAFF201401). We are grateful to Novartis for their financial support, especially Dr. Gunter Ostermann. We would also like to thank Dr. Michael Kharas for the helpful discussions during the preparation of the manuscript. F.J. was supported by a research grant from the Wilhelm-Sander Stiftung (2011.018.1). SK research is supported by a grant from the Deutsche José Carreras Leukämie-Stiftung Fund (DJCLS 10/23). We would also like to thank TIB MOLBIOL, Berlin, Germany, for designing MSI2 and HES1 probes and primers for the Taqman assay. KM and AC supported by a research grant from Leukaemia & Lymphoma NI.

Potential conflict of interest

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