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. 2015 Feb 3;3(1):e1009728.
doi: 10.1080/23723556.2015.1009728. eCollection 2016 Jan.

Regulation of hematopoietic progenitors by estrogens as a basis for new antileukemic strategies

Abel Sánchez-Aguilera  1 , Simón Méndez-Ferrer  1
Affiliations

Regulation of hematopoietic progenitors by estrogens as a basis for new antileukemic strategies

Abel Sánchez-Aguilera et al. Mol Cell Oncol. .

Abstract

We recently reported that estrogens regulate survival, proliferation, and self-renewal of hematopoietic stem cells and progenitors via estrogen receptor-α activation. Through its proapoptotic effect on malignant progenitors, tamoxifen treatment blocks the development of JAK2 (V617F) -induced myeloproliferative neoplasms in mice and sensitizes MLL-AF9-induced leukemias to chemotherapy, without detrimental effects on normal hematopoiesis.

Keywords: JAK2; MLL-AF9; acute myeloid leukemia; estrogen receptors; estrogens; hematopoietic progenitor cells; hematopoietic stem cells; myeloproliferative neoplasms; selective estrogen receptor modulators; tamoxifen.

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Figures

Figure 1.
Figure 1.
Tamoxifen selectively blocks JAK2V617F-induced myeloproliferative neoplasms. Hematologic parameters in peripheral blood of mice transplanted with Mx1-cre;JAK2V617F (top) or wild-type (WT, bottom) cells, treated with tamoxifen (TAM) or vehicle since the onset of thrombocytosis stage (9 weeks after transplantation). Tamoxifen doses (140 or 14 mg/kg, 3 times/week) are indicated. Data are means ± standard deviations. *P < 0.05 (vehicle versus tamoxifen). Both doses of tamoxifen abolish the leukocytosis, thrombocytosis, and reduction in red cell counts associated with progression of the disease. Data shown in this figure represent an extended follow-up of an experiment reported in Sánchez-Aguilera et al.
See this image and copyright information in PMC

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