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. 2022 Jan 17;9:813503. doi: 10.3389/fcell.2021.813503

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Copyright © 2022 Malcom, Ratri, Piasecka-Srader, Borosha, Chakravarthi, Alvarez, Vivian, Fields, Karim Rumi and Fields.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Inhibition of DOT1L methyltransferase activity with administration of EPZ-5676. Selective DOT1L methyltransferase inhibitor, EPZ-5676 (EPZ) was dissolved in 9:1, saline:ethanol and administered (30 μg/g body weight, intraperitoneally, twice daily) into 4-week old mice for 3 weeks (A). Age-matched control mice (Cont.) mice were injected with 9:1 saline:ethanol for the same duration. After 3 weeks, of EPZ-5676 or vehicle-treated mice were euthanized, and blood and bone marrow were collected. EPZ treatment significantly reduced H3K79 di-methylation in bone marrow cells (B,C). However, hemoglobin (Hb) levels were not decreased after EPZ treatment (D), and a peripheral blood film showed apparently minimal-to-no changes in the blood (E,F). RT-PCR analysis of expression of genes involved in blood development in bone marrow cells from Cont. or EPZ-treated mice showed no significant changes (G–L). Data presented as mean ± SEM, n ≥ 6, and * indicates p ≦ 0.05.