RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32DmiR-ON-221myeloblasts expressing wild type RUNX1. Second, with the same reporter system we assessed how these temporal dynamics are affected by the t(8;21)(q22;q22) acute myelogenous leukemia mutant RUNX1-MTG8 (RM8) in single 32D-RM8miR-ON-221myeloblasts. Depending on either wild type, or mutant, RUNX1 transcriptional regulation, the cell-context specific miR-221- regulated KIT level translates into differential single cell fate decisions. Collectively, single cell fate choices translate into either initial expansion of undifferentiated myeloblasts followed by terminal granulocyte differentiation, as it happens in normal granulopoiesis, or aggressive growth of undifferentiated myeloblasts, as it happens in RUNX1-MTG8-positive acute myelogenous leukemia. Increasing knowledge of biological changes, due to altered miRNA dynamics, is expected to have relevant translational implications for leukemia detection and treatment.

MiR-221-regulated KIT level by wild type or leukemia mutant RUNX1 : a determinant of single myeloblast fate decisions that - collectively - drives or hinders granulopoiesis / S. Rossetti, M.J. Anauo, N. Sacchi. - In: ONCOTARGET. - ISSN 1949-2553. - 8:49(2017), pp. 85783-85793. [10.18632/oncotarget.21266]

MiR-221-regulated KIT level by wild type or leukemia mutant RUNX1 : a determinant of single myeloblast fate decisions that - collectively - drives or hinders granulopoiesis

N. Sacchi
2017

Abstract

RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32DmiR-ON-221myeloblasts expressing wild type RUNX1. Second, with the same reporter system we assessed how these temporal dynamics are affected by the t(8;21)(q22;q22) acute myelogenous leukemia mutant RUNX1-MTG8 (RM8) in single 32D-RM8miR-ON-221myeloblasts. Depending on either wild type, or mutant, RUNX1 transcriptional regulation, the cell-context specific miR-221- regulated KIT level translates into differential single cell fate decisions. Collectively, single cell fate choices translate into either initial expansion of undifferentiated myeloblasts followed by terminal granulocyte differentiation, as it happens in normal granulopoiesis, or aggressive growth of undifferentiated myeloblasts, as it happens in RUNX1-MTG8-positive acute myelogenous leukemia. Increasing knowledge of biological changes, due to altered miRNA dynamics, is expected to have relevant translational implications for leukemia detection and treatment.
English
MiR-221-KIT axis; MiR-ON reporter; RUNX1-MTG8 mutant; Single myeloblast fate decisions; Wild type RUNX1; Oncology
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Pubblicazione scientifica
2017
Impact Journals
8
49
85783
85793
11
Pubblicato
Periodico con rilevanza internazionale
scopus
Aderisco
info:eu-repo/semantics/article
MiR-221-regulated KIT level by wild type or leukemia mutant RUNX1 : a determinant of single myeloblast fate decisions that - collectively - drives or hinders granulopoiesis / S. Rossetti, M.J. Anauo, N. Sacchi. - In: ONCOTARGET. - ISSN 1949-2553. - 8:49(2017), pp. 85783-85793. [10.18632/oncotarget.21266]
open
Prodotti della ricerca::01 - Articolo su periodico
3
262
Article (author)
no
S. Rossetti, M.J. Anauo, N. Sacchi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/623717
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