Author Correction: Mir142 loss unlocks IDH2R140-dependent leukemogenesis through antagonistic regulation of HOX genes

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

miR-142: A Master Regulator in Hematological Malignancies and Therapeutic Opportunities

“…Loss-of-function miR-142s were shown to synergize with the IDH2 R140Q mutation to cause leukemogenesis both in mice in vivo and in hematopoietic stem/progenitor cells in vitro [ 206 ]. Although complete miR-142 knockout in mice resulted in abnormally high levels of myeloblasts, these levels never exceeded 10% of bone marrow CD45+ cells to be considered leukemia development [ 206 ]. Similarly, complete miR-142 knockout or the IDH2 R140Q mutation alone did not cause the development of hematopoietic stem/progenitor cells into myeloid leukemia [ 206 ].…”

“…Although complete miR-142 knockout in mice resulted in abnormally high levels of myeloblasts, these levels never exceeded 10% of bone marrow CD45+ cells to be considered leukemia development [ 206 ]. Similarly, complete miR-142 knockout or the IDH2 R140Q mutation alone did not cause the development of hematopoietic stem/progenitor cells into myeloid leukemia [ 206 ]. The combined effect of loss-of-function miR-142 and IDH2 R140Q mutations can be potentially explained through the ability of miR-142 to counteract the slight IDH2 R140Q -caused downregulation of the pro-leukemic HOXA cluster, HOXA5 , HOXA7 , HOXA9 , and HOXA10 [ 206 ].…”

“…Similarly, complete miR-142 knockout or the IDH2 R140Q mutation alone did not cause the development of hematopoietic stem/progenitor cells into myeloid leukemia [ 206 ]. The combined effect of loss-of-function miR-142 and IDH2 R140Q mutations can be potentially explained through the ability of miR-142 to counteract the slight IDH2 R140Q -caused downregulation of the pro-leukemic HOXA cluster, HOXA5 , HOXA7 , HOXA9 , and HOXA10 [ 206 ]. The addition of the IDH2 R140Q mutation to loss-of-function miR-142 also upregulates MEIS1 and PBX3 , which are cofactors necessary for the upregulation of HOXA9 [ 206 ].…”

“…The combined effect of loss-of-function miR-142 and IDH2 R140Q mutations can be potentially explained through the ability of miR-142 to counteract the slight IDH2 R140Q -caused downregulation of the pro-leukemic HOXA cluster, HOXA5 , HOXA7 , HOXA9 , and HOXA10 [ 206 ]. The addition of the IDH2 R140Q mutation to loss-of-function miR-142 also upregulates MEIS1 and PBX3 , which are cofactors necessary for the upregulation of HOXA9 [ 206 ]. Upregulation of the HOXA cluster was shown to be at high levels in Mac1+ leukemic cells and was higher in Mac1+ myeloblasts compared to differentiated Mac1+ myeloid cells [ 206 ].…”

“…The addition of the IDH2 R140Q mutation to loss-of-function miR-142 also upregulates MEIS1 and PBX3 , which are cofactors necessary for the upregulation of HOXA9 [ 206 ]. Upregulation of the HOXA cluster was shown to be at high levels in Mac1+ leukemic cells and was higher in Mac1+ myeloblasts compared to differentiated Mac1+ myeloid cells [ 206 ]. Supporting the findings of Trissal et al, Marshall et al presented evidence that ASHL1 is an intermediate for miR-142 loss of function and IDH2 R140Q mutational activation of HOXA clusters for myeloid progenitor expansion, due to its ability to partially suppress colony formation in these double-mutated cells [ 206 ].…”