Currently, there are over 1,800 annotated human miRNAs, many of which have tissue-specific expression. Numerous studies have highlighted their role in haematopoietic differentiation and proliferation, acting as master regulators of haematopoietic stem cell function. Aberrant expression of miRNAs has been observed in haematological cancers, exhibiting unique expression signatures in comparison to normal counterparts. Functional and target analyses as well as animal models have attempted to annotate how different miRNA may contribute to the pathophysiology of these malignancies from modulating cancer associated genes, functioning directly as oncogenes or tumour suppressor genes or acting as bystanders or regulators of the epigenetic mechanisms in cancer. miRNAs have also been shown to play a role in modulating drug resistance and determining prognosis between the various subtypes of blood cancers. This review discusses the important role that miRNAs play in haematological malignancies by exploring associations that exist between the two and trying to examine evidence of causality to support the tantalising possibility that miRNAs might serve as therapeutic targets in blood cancers. 1. Introduction The haematological malignancies are a diverse group of neoplastic diseases. They are representing the fifth most common cancer in the UK and are among the twenty most common causes of cancer deaths in the UK [1]. A combination of clinical, cytogenetic, and genetic features and immunophenotype and cell morphology are used to stratify each of the haematological cancers further into subtypes [2]. Tumourigenesis has long been attributed to the alteration of oncogenes and tumour suppressor genes [3]. However, the discovery of non-protein-coding RNA, such as microRNAs (miRNAs) and their possible associations with cancer, has certified suspicions that tumour pathogenicity is far more complex than the simple deregulation of protein-coding genes and warrants further investigation. There are currently 1,862 miRNAs annotated in humans [4], most of which are evolutionarily conserved. miRNAs are 20–22 nucleotide transcripts in their mature form and function to inhibit gene expression via negative regulation of mRNA at a posttranscriptional level [5] (Figure 1). In vivo mice studies have illustrated that disruption of miRNA biogenesis through depletion of Dicer leads to embryological and developmental arrest and subsequent incompatibility with life [6]. miRNAs have since been demonstrated to be vital in other essential biological processes such as metabolism [5, 7],
References
[1]
Improving Outcomes in Haematological Cancers, National Institute for Clinical Excellence, 2003.
[2]
N. L. Harris, E. S. Jaffe, J. Diebold et al., “The world health organization classification-of hematological malignancies report of the clinical advisory committee meeting, Airlie House, Virginia, November 1997,” Modern Pathology, vol. 13, no. 2, pp. 193–207, 2000.
[3]
G. A. Calin and C. M. Croce, “MicroRNA signatures in human cancers,” Nature Reviews Cancer, vol. 6, no. 11, pp. 857–866, 2006.
[4]
miRBase, “Homosapiens miRNAs Release 20,” September 2013, http://www.mirbase.org/cgi-bin/mirna_summary.pl?org=hsa.
[5]
E. A. C. Wiemer, “The role of microRNAs in cancer: no small matter,” European Journal of Cancer, vol. 43, no. 10, pp. 1529–1544, 2007.
[6]
E. Bernstein, S. Y. Kim, M. A. Carmell et al., “Dicer is essential for mouse development,” Nature Genetics, vol. 35, no. 3, pp. 215–217, 2003.
[7]
M. N. Poy, L. Eliasson, J. Krutzfeldt et al., “A pancreatic islet-specific microRNA regulates insulin secretion,” Nature, vol. 432, no. 7014, pp. 226–230, 2004.
[8]
A. M. Cheng, M. W. Byrom, J. Shelton, and L. P. Ford, “Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis,” Nucleic Acids Research, vol. 33, no. 4, pp. 1290–1297, 2005.
[9]
P. Xu, M. Guo, and B. A. Hay, “MicroRNAs and the regulation of cell death,” Trends in Genetics, vol. 20, no. 12, pp. 617–624, 2004.
[10]
G. A. Calin, C. Sevignani, C. D. Dumitru et al., “Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 9, pp. 2999–3004, 2004.
[11]
R. I. Gregory and R. Shiekhattar, “MicroRNA biogenesis and cancer,” Cancer Research, vol. 65, no. 9, pp. 3509–3512, 2005.
[12]
M. S. Nicoloso, T. J. Kipps, C. M. Croce, and G. A. Calin, “MicroRNAs in the pathogeny of chronic lymphocytic leukaemia,” British Journal of Haematology, vol. 139, no. 5, pp. 709–716, 2007.
[13]
M. Mraz, S. Pospisilova, K. Malinova, I. Slapak, and J. Mayer, “MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes,” Leukemia and Lymphoma, vol. 50, no. 3, pp. 506–509, 2009.
[14]
G. A. Calin, C. D. Dumitru, M. Shimizu et al., “Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15524–15529, 2002.
[15]
A. Cimmino, G. A. Calin, M. Fabbri et al., “miR-15 and miR-16 induce apoptosis by targeting BCL2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 39, pp. 13944–13949, 2005.
[16]
U. Klein, M. Lia, M. Crespo et al., “The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia,” Cancer Cell, vol. 17, no. 1, pp. 28–40, 2010.
[17]
P. S. Linsley, J. Schelter, J. Burchard et al., “Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression,” Molecular and Cellular Biology, vol. 27, no. 6, pp. 2240–2252, 2007.
[18]
B. Zhang, X. Pan, G. P. Cobb, and T. A. Anderson, “microRNAs as oncogenes and tumor suppressors,” Developmental Biology, vol. 302, no. 1, pp. 1–12, 2007.
[19]
A. G. Knudson, “Hereditary cancer: theme and variations,” Journal of Clinical Oncology, vol. 15, no. 10, pp. 3280–3287, 1997.
[20]
E. S. Raveche, E. Salerno, B. J. Scaglione et al., “Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice,” Blood, vol. 109, no. 12, pp. 5079–5086, 2007.
[21]
G. A. Calin, M. Ferracin, A. Cimmono, et al., “A microRNA signature associated with prognosis and progression in chronic lymphocytic leukaemia,” The New England Journal of Medicine, vol. 353, no. 17, pp. 1793–1801, 2005.
[22]
J. Laine, G. Künstle, T. Obata, M. Sha, and M. Noguchi, “The protooncogene TCL1 is an Akt kinase coactivator,” Molecular Cell, vol. 6, no. 2, pp. 395–407, 2000.
[23]
Y. Pekarsky, U. Santanam, A. Cimmino et al., “Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181,” Cancer Research, vol. 66, no. 24, pp. 11590–11593, 2006.
[24]
M. Herling, K. A. Patel, J. Khalili et al., “TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state,” Leukemia, vol. 20, no. 2, pp. 280–285, 2006.
[25]
J. L. Mott, S. Kobayashi, S. F. Bronk, and G. J. Gores, “mir-29 regulates Mcl-1 protein expression and apoptosis,” Oncogene, vol. 26, no. 42, pp. 6133–6140, 2007.
[26]
V. Gandhi, K. Balakrishnan, and L. S. Chen, “McI-1: the 1 in CLL,” Blood, vol. 112, no. 9, pp. 3538–3540, 2008.
[27]
S. Debernardi, S. Skoulakis, G. Molloy, T. Chaplin, A. Dixon-McIver, and B. D. Young, “MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis,” Leukemia, vol. 21, no. 5, pp. 912–916, 2007.
[28]
M. Mraz, K. Malinova, J. Kotaskova et al., “miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities,” Leukemia, vol. 23, no. 6, pp. 1159–1163, 2009.
[29]
D. L. Zanette, F. Rivadavia, G. A. Molfetta et al., “miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia,” Brazilian Journal of Medical and Biological Research, vol. 40, no. 11, pp. 1435–1440, 2007.
[30]
T. Vergoulis, I. S. Vlachos, P. Alexiou, et al., “TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support,” Nucleic Acids Research, 2011.
[31]
D. Schotte, R. Pieters, and M. L. den Boer, “MicroRNAs in acute leukemia: from biological players to clinical contributors,” Leukemia, vol. 26, no. 1, pp. 1–12, 2012.
[32]
J. S. Rawlings, K. M. Rosler, and D. A. Harrison, “The JAK/STAT signaling pathway,” Journal of Cell Science, vol. 117, no. 8, pp. 1281–1283, 2004.
[33]
V. Fulci, S. Chiaretti, M. Goldoni et al., “Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia,” Blood, vol. 109, no. 11, pp. 4944–4951, 2007.
[34]
F. Rosenbauer, B. M. Owens, L. Yu et al., “Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1,” Nature Genetics, vol. 38, no. 1, pp. 27–37, 2006.
[35]
E. Pelosi, C. Labbaye, and U. Testa, “MicroRNAs in normal and malignant myelopoiesis,” Leukemia Research, vol. 33, no. 12, pp. 1584–1593, 2009.
[36]
X. Aggire, A. Jimenez-Velasco, E. San Jose-Eneriz, et al., “Hematopoietic tissue-specific has-miR-10a is down regulated in chronic myeloid leukaemia,” Molecular Cancer Research, vol. 6, pp. 1830–1840, 2008.
[37]
V. Scholl, R. Hassan, and I. R. Zalcberg, “MiRNA-451: a putative predictor marker of Imatinib therapy response in chronic myeloid leukemia,” Leukemia Research, vol. 36, no. 1, pp. 119–121, 2012.
[38]
L. Venturini, K. Battmer, M. Castoldi et al., “Expression of the miR-17-92 polycistron in Chronic Myeloid Leukemia (CML) CD34+ cells,” Blood, vol. 109, no. 10, pp. 4399–4405, 2007.
[39]
A. M. Eiring, J. G. Harb, P. Neviani et al., “miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts,” Cell, vol. 140, no. 5, pp. 652–665, 2010.
[40]
J. A. Chan, A. M. Krichevsky, and K. S. Kosik, “MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells,” Cancer Research, vol. 65, no. 14, pp. 6029–6033, 2005.
[41]
S. C. Ji, R. Santhanam, R. Trotta et al., “High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP-E2-dependent suppression of C/EBPα-driven myeloid differentiation,” Blood, vol. 110, no. 3, pp. 994–1003, 2007.
[42]
D. Perrotti, V. Cesi, R. Trotta et al., “BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2,” Nature Genetics, vol. 30, no. 1, pp. 48–58, 2002.
[43]
D. Perrotti and P. Neviani, “From mRNA metabolism to cancer therapy: chronic myelogenous leukemia shows the way,” Clinical Cancer Research, vol. 13, no. 6, pp. 1638–1642, 2007.
[44]
S. Scholl, H.-J. Fricke, H. G. Sayer, and K. H？ffken, “Clinical implications of molecular genetic aberrations in acute myeloid leukemia,” Journal of Cancer Research and Clinical Oncology, vol. 135, no. 4, pp. 491–505, 2009.
[45]
S. Mi, J. Lu, M. Sun et al., “MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 50, pp. 19971–19976, 2007.
[46]
K. Mrózek, D. P. Harper, and P. D. Aplan, “Cytogenetics and molecular genetics of acute lymphoblastic leukemia,” Hematology/Oncology Clinics of North America, vol. 23, no. 5, pp. 991–1010, 2009.
[47]
B. Johansson, F. Mertens, and F. Mitelman, “Clinical and biological importance of cytogenetic abnormalities in childhood and adult acute lymphoblastic leukemia,” Annals of Medicine, vol. 36, no. 7, pp. 492–503, 2004.
[48]
F. Mitelman, B. Johansson, and F. Mertens, Eds., “Mitelman database of chromosome aberrations in cancer,” 2003, http://cgap.nci.nih.gov/Chromosomes/Mitelman.
[49]
J. C. de Oliveira, C. A. Scrideli, M. S. Brassesco et al., “Differential MiRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features,” Leukemia Research, vol. 36, no. 3, pp. 293–298, 2012.
[50]
A. Dixon-McIver, P. East, C. A. Mein et al., “Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia,” PLoS ONE, vol. 3, no. 5, Article ID e2141, 2008.
[51]
M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. L？wenberg, “MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia,” Blood, vol. 111, no. 10, pp. 5078–5085, 2008.
[52]
R. Garzon, M. Garofalo, M. P. Martelli et al., “Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 10, pp. 3945–3950, 2008.
[53]
S. Debernardi, S. Skoulakis, G. Molloy, T. Chaplin, A. Dixon-McIver, and B. D. Young, “MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis,” Leukemia, vol. 21, no. 5, pp. 912–916, 2007.
[54]
R. Garzon, F. Pichiorri, T. Palumbo et al., “MicroRNA fingerprints during human megakaryocytopoiesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 13, pp. 5078–5083, 2006.
[55]
N. Shah and S. Sukumar, “The Hox genes and their roles in oncogenesis,” Nature Reviews Cancer, vol. 10, no. 5, pp. 361–371, 2010.
[56]
T. R. Golub, D. K. Slonim, P. Tamayo et al., “Molecular classification of cancer: class discovery and class prediction by gene expression monitoring,” Science, vol. 286, no. 5439, pp. 531–527, 1999.
[57]
R. Garzon, C. E. A. Heaphy, V. Havelange et al., “MicroRNA 29b functions in acute myeloid leukemia,” Blood, vol. 114, no. 26, pp. 5331–5341, 2009.
[58]
S. K. Zaidi, C. R. Dowdy, A. J. van Wijnen et al., “Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network,” Cancer Research, vol. 69, no. 21, pp. 8249–8255, 2009.
[59]
S.-M. Gao, C.-Y. Xing, C.-Q. Chen, S.-S. Lin, P.-H. Dong, and F.-J. Yu, “MiR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level,” Journal of Experimental and Clinical Cancer Research, vol. 30, no. 1, article 110, 2011.
[60]
G. A. Calin, A. Cimmino, M. Fabbri et al., “MiR-15a and miR-16-1 cluster functions in human leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 13, pp. 5166–5171, 2008.
[61]
D. Schotte, R. X. de Menezes, F. A. Moqadam et al., “MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia,” Haematologica, vol. 96, no. 5, pp. 703–711, 2011.
[62]
P. Wong, M. Iwasaki, T. C. P. Somervaille et al., “The miR-17-92 microRNA polycistron regulates MLL leukemia stem cell potential by modulating p21 expression,” Cancer Research, vol. 70, no. 9, pp. 3833–3842, 2010.
[63]
K. J. Mavrakis, A. L. Wolfe, E. Oricchio et al., “Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia,” Nature Cell Biology, vol. 12, no. 4, pp. 372–379, 2010.
[64]
M. Fabbri, R. Garzon, M. Andreeff, H. M. Kantarjian, G. Garcia-Manero, and G. A. Calin, “MicroRNAs and noncoding RNAs in hematological malignancies: molecular, clinical and therapeutic implications,” Leukemia, vol. 22, no. 6, pp. 1095–1105, 2008.
[65]
L. He, J. M. Thomson, M. T. Hemann et al., “A microRNA polycistron as a potential human oncogene,” Nature, vol. 435, no. 7043, pp. 828–833, 2005.
[66]
C. Xiao, L. Srinivasan, D. P. Calado et al., “Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes,” Nature Immunology, vol. 9, no. 4, pp. 405–414, 2008.
[67]
K. A. O'Donnell, E. A. Wentzel, K. I. Zeller, C. V. Dang, and J. T. Mendell, “c-Myc-regulated microRNAs modulate E2F1 expression,” Nature, vol. 435, no. 7043, pp. 839–843, 2005.
[68]
A. P. Bracken, M. Ciro, A. Cocito, and K. Helin, “E2F target genes: unraveling the biology,” Trends in Biochemical Sciences, vol. 29, no. 8, pp. 409–417, 2004.
[69]
I. Matsumura, H. Tanaka, and Y. Kanakura, “E2F1 and c-Myc in cell growth and death,” Cell Cycle, vol. 2, no. 4, pp. 333–338, 2003.
[70]
W. Tam, “Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA,” Gene, vol. 274, no. 1-2, pp. 157–167, 2001.
[71]
P. S. Eis, W. Tam, L. Sun et al., “Accumulation of miR-155 and BIC RNA in human B cell lymphomas,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 10, pp. 3627–3632, 2005.
[72]
M. Wang, L. P. Tan, M. K. Dijkstra et al., “miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression,” Journal of Pathology, vol. 215, no. 1, pp. 13–20, 2008.
[73]
S. Costinean, N. Zanesi, Y. Pekarsky et al., “Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 18, pp. 7024–7029, 2006.
[74]
B. John, A. J. Enright, A. Aravin, T. Tuschl, C. Sander, and D. S. Marks, “Human microRNA targets,” PLoS Biology, vol. 2, no. 11, article e363, 2004.
[75]
R. Garzon, M. Fabbri, A. Cimmino, G. A. Calin, and C. M. Croce, “MicroRNA expression and function in cancer,” Trends in Molecular Medicine, vol. 12, no. 12, pp. 580–587, 2006.
[76]
F. Pichiorri, S.-S. Suh, M. Ladetto et al., “MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 35, pp. 12885–12890, 2008.
[77]
F. Pichiorri, L. de Luca, and R. I. Aqeilan, “MicroRNAs: new players in multiple myeloma,” Frontiers in Genetics, vol. 2: article 22, 2011.
[78]
D. L？ffler, K. Brocke-Heidrich, G. Pfeifer et al., “Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer,” Blood, vol. 110, no. 4, pp. 1330–1333, 2007.
[79]
F. Petrocca, A. Vecchione, and C. M. Croce, “Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor β signaling,” Cancer Research, vol. 68, no. 20, pp. 8191–8194, 2008.
[80]
A. M. Roccaro, A. Sacco, B. Thompson et al., “MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma,” Blood, vol. 113, no. 26, pp. 6669–6680, 2009.
[81]
S. L. Corthals, M. Jongen-Lavrencic, Y. de Knegt et al., “Micro-RNA-15a and micro-RNA-16 expression and chromosome 13 deletions in multiple myeloma,” Leukemia Research, vol. 34, no. 5, pp. 677–681, 2010.
[82]
M. Lionetti, L. Agnelli, L. Mosca et al., “Integrative high-resolution microarray analysis of human myeloma cell lines reveals deregulated miRNA expression associated with allelic imbalances and gene expression profiles,” Genes Chromosomes and Cancer, vol. 48, no. 6, pp. 521–531, 2009.
[83]
S. Stilgenbauer, J. Nickolenko, J. Wilhelm et al., “Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma,” Oncogene, vol. 16, no. 14, pp. 1891–1897, 1998.
[84]
J.-T. Dong, J. C. Boyd, and H. F. Frierson Jr., “Loss of heterozygosity at 13q14 and 13q21 in high grade, high stage prostate cancer,” Prostate, vol. 49, no. 3, pp. 166–171, 2001.
[85]
T. Schmidt and P. Carmeliet, “Angiogenesis: a target in solid tumors, also in leukemia?” American Society of Hematology. Education Program, vol. 2011, pp. 1–8, 2011.
[86]
M. Dews, A. Homayouni, D. Yu et al., “Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster,” Nature Genetics, vol. 38, no. 9, pp. 1060–1065, 2006.
[87]
Z. Hua, Q. Lv, W. Ye, et al., “MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia,” PLoS ONE, vol. 1, no. 1, article e116, 2006.
[88]
“National Cancer Institute: Metastatic Cancer,” May 2011, http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic.
[89]
A. Lujambio and M. Esteller, “CpG island hypermethylation of tumor suppressor microRNAs in human cancer,” Cell Cycle, vol. 6, no. 12, pp. 1455–1459, 2007.
[90]
B. Weber, C. Stresemann, B. Brueckner, and F. Lyko, “Methylation of human MicroRNA genes in normal and neoplastic cells,” Cell Cycle, vol. 6, no. 9, pp. 1001–1005, 2007.
[91]
X. Agirre, J. á. Martínez-Climent, M. D. Odero, and F. Prósper, “Epigenetic regulation of miRNA genes in acute leukemia,” Leukemia, vol. 26, no. 3, pp. 395–403, 2012.
[92]
C. S. Chim, K. Y. Wong, Y. Qi et al., “Epigenetic inactivation of the miR-34a in hematological malignancies,” Carcinogenesis, vol. 31, no. 4, pp. 745–750, 2010.
[93]
D. J. P. M. Stumpel, D. Schotte, E. A. M. Lange-Turenhout et al., “Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale,” Leukemia, vol. 25, no. 3, pp. 429–439, 2011.
[94]
G. Marcucci, K. S. Maharry, K. H. Metzeler, et al., “Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients,” Journal of Clinical Oncology, vol. 31, no. 17, pp. 2086–2093, 2013.
[95]
Y. Chen, R. Jacomo, M. Konopleva, et al., “CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia,” The Journal of Clinical Investigation, vol. 123, no. 6, pp. 2395–2407, 2013.
[96]
N. Mosakhani, R. Raty, A. Tvybakinoia, M. L. Karjalainen-Lindsberg, E. Elonen, and S. Knuutila, “MicroRNA profiling in chemoresistant and chemosensitive acute myeloid leukemia,” Cytogenetic and Genome Research, vol. 141, pp. 272–276, 2013.
[97]
R. Garzon and C. M. Croce, “MicroRNAs in normal and malignant hematopoiesis,” Current Opinion in Hematology, vol. 15, no. 4, pp. 352–358, 2008.
[98]
T. Bammler, R. P. Beyer, S. Bhattacharya, et al., “Standardizing global gene expression analysis between laboratories and across platforms,” Nature Methods, vol. 2, no. 5, pp. 351–356, 2005.
[99]
A. Mencía, S. Modamio-H？ybj？r, N. Redshaw, et al., “Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss,” Nature Genetics, vol. 41, no. 5, pp. 609–613, 2009.
[100]
Q. Jing, S. Huang, S. Guth et al., “Involvement of microRNA in AU-rich element-mediated mRNA instability,” Cell, vol. 120, no. 5, pp. 623–634, 2005.
[101]
G. Bejerano, M. Pheasant, I. Makunin et al., “Ultraconserved elements in the human genome,” Science, vol. 304, no. 5675, pp. 1321–1325, 2004.
[102]
P. Mestdagh, E. Fredlund, F. Pattyn et al., “An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours,” Oncogene, vol. 29, no. 24, pp. 3583–3592, 2010.
[103]
G. A. Calin, C.-G. Liu, M. Ferracin et al., “Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas,” Cancer Cell, vol. 12, no. 3, pp. 215–229, 2007.
[104]
C. Taccioli, E. Fabbri, R. Visone et al., “UCbase & miRfunc: a database of ultraconserved sequences and microRNA function,” Nucleic Acids Research, vol. 37, no. 1, pp. D41–D48, 2009.
