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Editorial
. 2020 Sep 1;105(9):2188-2189.
doi: 10.3324/haematol.2020.254474.

Novel use for selective inhibitors of nuclear export in β-thalassemia: block of HSP70 export from the nucleus via exportin Xpo1 improves ineffective erythropoiesis

Susree Modepalli  1 , Shilpa M Hattangadi  2
Affiliations
Editorial

Novel use for selective inhibitors of nuclear export in β-thalassemia: block of HSP70 export from the nucleus via exportin Xpo1 improves ineffective erythropoiesis

Susree Modepalli et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
KPT-251 inhibition of HSP70 export from the nucleus via exportin Xpo1 improves ineffective erythropoiesis in β-thalassemia. Under normal conditions, nuclear HSP70 protects GATA1 from caspase-3 cleavage. In thalassemia, excess free a-globin chains sequester HSP70 in the cytoplasm, prevent normal GATA1 target expression, and result in ineffective erythropoiesis. Treating erythroblasts with the Xpo1 inhibitor KPT-251 increases nuclear levels of HSP70, rescues GATA1 from caspase-3 cleavage, and improves terminal erythroid development.
See this image and copyright information in PMC

Comment on

  • XPO1 regulates erythroid differentiation and is a new target for the treatment of β-thalassemia.
    Guillem F, Dussiot M, Colin E, Suriyun T, Arlet JB, Goudin N, Marcion G, Seigneuric R, Causse S, Gonin P, Gastou M, Deloger M, Rossignol J, Lamarque M, Choucair ZB, Gautier EF, Ducamp S, Vandekerckhove J, Moura IC, Maciel TT, Garrido C, An X, Mayeux P, Mohandas N, Courtois G, Hermine O. Guillem F, et al. Haematologica. 2020 Sep 1;105(9):2240-2249. doi: 10.3324/haematol.2018.210054. Haematologica. 2020. PMID: 33054049 Free PMC article.

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