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Chronic lymphocytic leukemia

Blood cancer driver Musashi-2 as therapeutic target in chronic lymphocytic leukemia

Leukemia volume 35, pages 982–983 (2021)Cite this article

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In this issue of Leukemia, Palacios et al. [1] established a functional role for Musashi 2 in chronic lymphocytic leukemia (CLL) and demonstrated its implication in driving the proliferative fraction of CLL cells. CLL is regarded as an incurable disease showing a generally indolent, though highly variable clinical course. This variability can be estimated by prognostic markers such as IGHV mutational status, cytogenetics, and TP53 mutations [2]. Recently, novel therapeutic strategies such as B cell receptor blockers and the bcl-2 inhibitor venetoclax have revolutionized the field of CLL [3]. However, virtually all patients eventually relapse, presumably by evolution and selection of aggressive clones [4].

RNA protein binding Musashi (MSI) is named after the legendary Japanese swordsman Miyamoto Musashi (1584–1645) renowned for his unique double-bladed fighting style, since MSI mutations in Drosophila resulted in two shafts of a single mechanosensory bristle [5]. The mammalian counterparts of this evolutionary conserved gene, Musashi-1 (MSI1) and Musashi-2 (MSI2), act as translational inhibitors and have important roles in self-renewal and differentiation processes. Both have also been implicated in multiple types of cancers, including leukemias. In contrast to MSI1, MSI2 is a critical regulator of hematopoietic stem cells, with MSI2 deletion leading to a decrease in hematopoietic stem cells, and its overexpression to an increase in progenitor and stem cells [6, 7]. This remarkable ancient program is able to compensate loss of progenitor cells from dormant stem cells, however, when unleashed, it has the potential to propagate very aggressive forms of leukemia.

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References

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  1. Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria

    Lukas Kazianka & Philipp B. Staber

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  1. Lukas Kazianka
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Correspondence to Philipp B. Staber.

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Kazianka, L., Staber, P.B. Blood cancer driver Musashi-2 as therapeutic target in chronic lymphocytic leukemia. Leukemia 35, 982–983 (2021). https://doi.org/10.1038/s41375-021-01144-1

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