alexa Targeting Protein Arginine Methyltransferase 1 Blocks RBM15-MKL1 Fusion-Initiated Human Stem Cell Transformation | OMICS International | Abstract
ISSN: 2165-7831

Journal of Blood & Lymph
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Research Article

Targeting Protein Arginine Methyltransferase 1 Blocks RBM15-MKL1 Fusion-Initiated Human Stem Cell Transformation

Jin S1,2, Yao Z2, Mi Y3, Wang H2, Yao S2, Song J1, Zhang P3, Zhang J2, Zhou W2, Ma J4, Guo Y4 and Liu Y2*

1Department of Internal Medicine, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Internal Medicine, Henan Cancer Hospital and Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

3Department of Otolaryngology and Head Neck Surgery, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China

4Department of Molecular Pathology, Henan Cancer Hospital and Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

*Corresponding Author:
Liu Y
Department of Internal Medicine
Henan Cancer Hospital & Affiliated Cancer Hospital of Zhengzhou University
Zhengzhou, China
Tel: 0086-371-65587791
E-mail: [email protected]

Received Date: February 20, 2017; Accepted Date: March 10, 2017; Published Date: March 15, 2017

Citation: Jin S, Yao Z, Mi Y, Wang H, Yao S, et al. (2017) Targeting Protein Arginine Methyltransferase 1 Blocks RBM15-MKL1 Fusion-Initiated Human Stem Cell Transformation. J Blood Lymph 7: 158. doi: 10.4172/2165-7831.1000158

Copyright: © 2017 Jin S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: The chromosome translocation t (1;22), which generates the RBM15-MKL1 fusion gene, is found in approximately 10% of pediatric acute megakaryoblastic leukemia cases. Given that PRMT1 downregulation is critical for megakaryocyte differentiation, we propose the use of the PRMT1 inhibitor furamidine to stimulate RBM15- MKL1-transformed human cord blood cells to undergo megakaryocyte differentiation. Materials and methods: Human CD34+ cells were purified from umbilical cord blood with anti-CD34 magnetic beads. Lentivirus-infected CD34+ cells were sorted using flow cytometry. The methylcellulose colony replating assay was performed to evaluate the transformation efficiency. Cell viability was calculated using a CellTiter-Glo® luminescent cell viability assay kit. Results: The simultaneous transduction of RBM15-MKL1 and MPLW515L, a mutated MPL gene found in AMKL patients, into human CD34+ cells resulted in long-term growth in the presence of a cytokine mix that maintains a population of hematopoietic stem progenitor cells. Elevated expression of PRMT1 was detected in cells transduced with RBM15-MKL1 together with MPLW515L. The PRMT1 inhibitor furamidine (aka DB75) reversed the inhibition of RBM15-MKL1-mediated megakaryocytic differentiation and impeded the replating capability of the transformed cells. Conclusion: PRMT1 facilitates the transformation induced by RBM15-MKL1, and inhibiting PRMT1 activity promotes MK differentiation. Given that furamidine has been used for treating trypanosomiasis in clinical trials and proven to be safe, using furamidine to treat AMKL may be a new curative option for RBM15-MKL1-associated leukemia.

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