Musashi 2 influences chronic lymphocytic leukemia cell survival and growth making it a potential therapeutic target Journal Article

Authors: Palacios, F.; Yan, X. J.; Ferrer, G.; Chen, S. S.; Vergani, S.; Yang, X.; Gardner, J.; Barrientos, J. C.; Rock, P.; Burack, R.; Kolitz, J. E.; Allen, S. L.; Kharas, M. G.; Abdel-Wahab, O.; Rai, K. R.; Chiorazzi, N.
Article Title: Musashi 2 influences chronic lymphocytic leukemia cell survival and growth making it a potential therapeutic target
Abstract: Progression of chronic lymphocytic leukemia (CLL) results from the expansion of a small fraction of proliferating leukemic B cells. When comparing the global gene expression of recently divided CLL cells with that of previously divided cells, we found higher levels of genes involved in regulating gene expression. One of these was the oncogene Musashi 2 (MSI2), an RNA-binding protein that induces or represses translation. While there is an established role for MSI2 in normal and malignant stem cells, much less is known about its expression and role in CLL. Here we report for the first time ex vivo and in vitro experiments that MSI2 protein levels are higher in dividing and recently divided leukemic cells and that downregulating MSI2 expression or blocking its function eliminates primary human and murine CLL and mature myeloid cells. Notably, mature T cells and hematopoietic stem and progenitor cells are not affected. We also confirm that higher MSI2 levels correlate with poor outcome markers, shorter time-to-first-treatment, and overall survival. Thus, our data highlight an important role for MSI2 in CLL-cell survival and proliferation and associate MSI2 with poor prognosis in CLL patients. Collectively, these findings pinpoint MSI2 as a potentially valuable therapeutic target in CLL. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: controlled study; protein expression; unclassified drug; human cell; overall survival; nonhuman; t lymphocyte; animal cell; mouse; animal tissue; cell survival; cell division; cell growth; cell maturation; animal experiment; animal model; in vitro study; rna binding protein; bone marrow cell; hematopoietic stem cell; ex vivo study; chronic lymphatic leukemia; cancer prognosis; time to treatment; human; priority journal; article; musashi 2; chronic lymphoid leukemia cell line
Journal Title: Leukemia
Volume: 35
Issue: 4
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2021-04-01
Start Page: 1037
End Page: 1052
Language: English
DOI: 10.1038/s41375-020-01115-y
PUBMED: 33504942
PROVIDER: scopus
PMCID: PMC8024198
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Jeffrey Gardner
    34 Gardner
  2. Michael Kharas
    66 Kharas
  3. Xuejing Yang
    3 Yang