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Open Access 01-12-2011 | Short report

Differential Expression of MicroRNAs in CD34+ Cells of 5q- Syndrome

Authors: Hana Votavova, Martina Grmanova, Michaela Dostalova Merkerova, Monika Belickova, Alzbeta Vasikova, Radana Neuwirtova, Jaroslav Cermak

Published in: Journal of Hematology & Oncology | Issue 1/2011

Abstract

Background

Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Further, we studied gene expressions of miR-143, miR-145, miR-378 and miR-146a mapped within the 5q deletion.

Results

Using microarrays we identified 21 differently expressed miRNAs in 5q- patients compared to controls. Especially, miR-34a was markedly overexpressed in 5q- patients, suggesting its role in an increased apoptosis of bone marrow progenitors. Out of four miRNAs at del(5q), only miR-378 and miR-146a showed reduced gene expression in the patients. An integrative analysis of mRNA profiles and predicted putative targets defined potential downstream targets of the deregulated miRNAs. The list of targets included several genes that play an important role in the regulation of hematopoiesis (e.g. KLF4, LEF1, SPI1).

Conclusions

The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage.

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Bruchova H, Merkerova M, Prchal JT: Aberrant expression of microRNA in polycythemia vera. Haematologica. 2008, 93: 1009-1016. 10.3324/haematol.12706.CrossRefPubMed

Guglielmelli P, Tozzi L, Pancrazzi A, Bogani C, Antonioli E, Ponziani V, Poli G, Zini R, Ferrari S, Manfredini R, Bosi A, Vannucchi AM, MPD Research Consortium: MicroRNA expression profile in granulocytes from primary myelofibrosis patients. Exp Hematol. 2007, 35: 1708-1718. 10.1016/j.exphem.2007.08.020.CrossRefPubMed

Pons A, Nomdedeu B, Navarro A, Gaya A, Gel B, Diaz T, Valera S, Rozman M, Belkaid M, Montserrat E, Monzo M: Hematopoiesis-related microRNA expression in myelodysplastic syndromes. Leuk Lymphoma. 2009, 14: 1-6. 10.1080/10428190903147645.CrossRef

Hussein K, Theophile K, Büsche G, Schlegelberger B, Göhring G, Kreipe H, Bock O: Aberrant microRNA expression pattern in myelodysplastic bone marrow cells. Leuk Res. 2010, 34: 1169-1174. 10.1016/j.leukres.2010.04.012.CrossRefPubMed

Vasikova A, Belickova M, Budinska E, Cermak J: A distinct expression of various gene subsets in CD34+ cells from patients with early and advanced myelodysplastic syndrome. Leuk Res. 2010, 34: 1566-1572. 10.1016/j.leukres.2010.02.021.CrossRefPubMed

Shen WF, Hu YL, Uttarwar L, Passegue E, Largman C: MicroRNA-126 regulates HOXA9 by binding to the homeobox. Mol Cell Biol. 2008, 28: 4609-4619. 10.1128/MCB.01652-07.PubMedCentralCrossRefPubMed

Poppe B, Vandesompele J, Schoch C, Lindvall C, Mrozek K, Bloomfield CD, Beverloo HB, Michaux L, Dastugue N, Herens C, Yigit N, De Paepe A, Hagemeijer A, Speleman F: Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies. Blood. 2004, 103: 229-235. 10.1182/blood-2003-06-2163.CrossRefPubMed

Thorsteinsdottir U, Mamo A, Kroon E, Jerome L, Bijl J, Lawrence HJ, Humphries K, Sauvageau G: Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood. 2002, 99: 121-129. 10.1182/blood.V99.1.121.CrossRefPubMed

Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007, 26: 745-752. 10.1016/j.molcel.2007.05.010.PubMedCentralCrossRefPubMed

10.

Bruchova H, Yoon D, Agarwal AM, Mendell J, Prchal JT: Regulated expression of miRNAs in normal and polycythemia vera erythropoiesis. Exp Hematol. 2007, 35: 1657-1667. 10.1016/j.exphem.2007.08.021.PubMedCentralCrossRefPubMed

11.

Pase L, Layton JE, Kloosterman WP, Carradice D, Waterhouse PM, Lieschke GJ: miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2. Blood. 2009, 113: 1794-1804. 10.1182/blood-2008-05-155812.PubMedCentralCrossRefPubMed

12.

Pulikkan JA, Dengler V, Peramangalam PS, Peer Zada AA, Müller-Tidow C, Bohlander SK, Tenen DG, Behre G: Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood. 2010, 115: 1768-1778. 10.1182/blood-2009-08-240101.PubMedCentralCrossRefPubMed

13.

Felli N, Pedini F, Romania P, Biffoni M, Morsilli O, Castelli G, Santoro S, Chicarella S, Sorrentino A, Peschle C, Marziali G: MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis. Haematologica. 2009, 94: 479-486. 10.3324/haematol.2008.002345.PubMedCentralCrossRefPubMed

14.

Bousquet M, Quelen C, Rosati R, Mansat-De Mas V, La Starza R, Bastard C, Lippert E, Talmant P, Lafage-Pochitaloff M, Leroux D, Gervais C, Viguié F, Lai JL, Terre C, Beverlo B, Sambani C, Hagemeijer A, Marynen P, Delsol G, Dastugue N, Mecucci C, Brousset P: Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. J Exp Med. 2008, 205: 2499-506. 10.1084/jem.20080285.PubMedCentralCrossRefPubMed

15.

Guo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, Purton LE, Fleming HH, Cobb B, Merkenschlager M, Golub TR, Scadden DT: MicroRNA miR-125a controls hematopoietic stem cell number. Proc Natl Acad Sci USA. 2010, 107: 14229-14234. 10.1073/pnas.0913574107.PubMedCentralCrossRefPubMed

16.

Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, Bohlander SK, Le Beau MM, Larson RA, Golub TR, Rowley JD, Chen J: MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 2007, 104: 19971-19976. 10.1073/pnas.0709313104.PubMedCentralCrossRefPubMed

17.

Kotani A, Ha D, Hsieh J, Rao PK, Schotte D, den Boer ML, Armstrong SA, Lodish HF: miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221. Blood. 2009, 114: 4169-4178. 10.1182/blood-2008-12-191619.PubMedCentralCrossRefPubMed

18.

De Marchis ML, Ballarino M, Salvatori B, Puzzolo MC, Bozzoni I, Fatica A: A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells. Leukemia. 2009, 23: 856-862. 10.1038/leu.2008.372.CrossRefPubMed

19.

Boultwood J, Pellagatti A, Cattan H, Lawrie CH, Giagounidis A, Malcovati L, Della Porta MG, Jädersten M, Killick S, Fidler C, Cazzola M, Hellström-Lindberg E, Wainscoat JS: Gene expression profiling of CD34+ cells in patients with the 5q- syndrome. Br J Haematol. 2007, 139: 578-589. 10.1111/j.1365-2141.2007.06833.x.CrossRefPubMed

20.

Starczynowski DT, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells RA, Buckstein R, Lam W, Humphries RK, Karsan A: Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med. 2010, 16: 49-58. 10.1038/nm.2054.CrossRefPubMed

21.

Feinberg MW, Wara AK, Cao Z, Lebedeva MA, Rosenbauer F, Iwasaki H, Hirai H, Katz JP, Haspel RL, Gray S, Akashi K, Segre J, Kaestner KH, Tenen DG, Jain MK: The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO J. 2007, 26: 4138-4148. 10.1038/sj.emboj.7601824.PubMedCentralCrossRefPubMed

22.

Skokowa J, Cario G, Uenalan M, Schambach A, Germeshausen M, Battmer K, Zeidler C, Lehmann U, Eder M, Baum C, Grosschedl R, Stanulla M, Scherr M, Welte K: LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia. Nat Med. 2006, 12: 1191-1197. 10.1038/nm1474.CrossRefPubMed

Title: Differential Expression of MicroRNAs in CD34+ Cells of 5q- Syndrome
Authors: Hana Votavova
Martina Grmanova
Michaela Dostalova Merkerova
Monika Belickova
Alzbeta Vasikova
Radana Neuwirtova
Jaroslav Cermak
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2011
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/1756-8722-4-1

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