Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2016

Open Access 01-12-2016 | Research

GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

Authors: Laura Guerenne, Stéphanie Beurlet, Mohamed Said, Petra Gorombei, Carole Le Pogam, Fabien Guidez, Pierre de la Grange, Nader Omidvar, Valérie Vanneaux, Ken Mills, Ghulam J Mufti, Laure Sarda-Mantel, Maria Elena Noguera, Marika Pla, Pierre Fenaux, Rose Ann Padua, Christine Chomienne, Patricia Krief

Published in: Journal of Hematology & Oncology | Issue 1/2016

Login to get access

Abstract

Background

In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease.

Methods

We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively.

Results

Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples.

Conclusions

These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.
Appendix
Available only for authorised users
Literature
1.
Mughal TI, Cross NC, Padron E, Tiu RV, Savona M, Malcovati L, et al. An International MDS/MPN Working Group’s perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms. Haematologica. 2015;100(9):1117–30.CrossRefPubMed
2.
3.
4.
Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241–7.PubMedCentralCrossRefPubMed
5.
Hajkova H, Fritz MH, Haskovec C, Schwarz J, Salek C, Markova J, et al. CBFB-MYH11 hypomethylation signature and PBX3 differential methylation revealed by targeted bisulfite sequencing in patients with acute myeloid leukemia. J Hematol Oncol. 2014;7:66.PubMedCentralCrossRefPubMed
6.
Malcovati L, Papaemmanuil E, Ambaglio I, Elena C, Galli A, Della Porta MG, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014;124(9):1513–21.PubMedCentralCrossRefPubMed
7.
Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Peng J, Tang G, et al. TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol. 2015;8:45.PubMedCentralCrossRefPubMed
8.
Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van LP, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27.PubMedCentralCrossRefPubMed
9.
Skvarova KK, Fiser K, Mejstrikova E, Rejlova K, Zaliova M, Fornerod M, et al. Homeobox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations. J Hematol Oncol. 2014;7:94.CrossRef
10.
Visconte V, Tabarroki A, Zhang L, Parker Y, Hasrouni E, Mahfouz R, et al. Splicing factor 3b subunit 1 (Sf3b1) haploinsufficient mice display features of low risk Myelodysplastic syndromes with ring sideroblasts. J Hematol Oncol. 2014;7:89.PubMedCentralCrossRefPubMed
11.
12.
Chen G, Zeng W, Miyazato A, Billings E, Maciejewski JP, Kajigaya S, et al. Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities. Blood. 2004;104(13):4210–8.CrossRefPubMed
13.
Del Rey M, O’Hagan K, Dellett M, Aibar S, Colyer HA, Alonso ME, et al. Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes. Leukemia. 2013;27(3):610–8.CrossRefPubMed
14.
Dellett M, O’Hagan KA, Colyer HA, Mills KI. Identification of gene networks associated with acute myeloid leukemia by comparative molecular methylation and expression profiling. Biomark Cancer. 2010;2:43–55.PubMedCentralPubMed
15.
Dolatshad H, Pellagatti A, Fernandez-Mercado M, Yip BH, Malcovati L, Attwood M, et al. Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells. Leukemia. 2015;29(5):1092–103.PubMedCentralCrossRefPubMed
16.
Galili N, Raza A. Clinical implications of gene expression profiling in myelodysplastic syndromes: recognition of ribosomal and translational gene dysregulation and development of predictive assays. Best Pract Res Clin Haematol. 2009;22(2):223–37.CrossRefPubMed
17.
Gerstung M, Pellagatti A, Malcovati L, Giagounidis A, Porta MG, Jadersten M, et al. Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes. Nat Commun. 2015;6:5901.PubMedCentralCrossRefPubMed
18.
Hofmann WK, de Vos S, Komor M, Hoelzer D, Wachsman W, Koeffler HP. Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow. Blood. 2002;100(10):3553–60.CrossRefPubMed
19.
Li L, Li M, Sun C, Francisco L, Chakraborty S, Sabado M, et al. Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk. Cancer Cell. 2011;20(5):591–605.PubMedCentralCrossRefPubMed
20.
Pellagatti A, Cazzola M, Giagounidis A, Perry J, Malcovati L, Della Porta MG, et al. Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells. Leukemia. 2010;24(4):756–64.CrossRefPubMed
21.
Pellagatti A, Benner A, Mills KI, Cazzola M, Giagounidis A, Perry J, et al. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J Clin Oncol. 2013;31(28):3557–64.CrossRefPubMed
22.
Sridhar K, Ross DT, Tibshirani R, Butte AJ, Greenberg PL. Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression. Blood. 2009;114(23):4847–58.PubMedCentralCrossRefPubMed
23.
Taskesen E, Havermans M, van Lom K, Sanders MA, van Norden Y, Bindels E, et al. Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling. Blood. 2014;123(21):3327–35.CrossRefPubMed
24.
Theilgaard-Monch K, Boultwood J, Ferrari S, Giannopoulos K, Hernandez-Rivas JM, Kohlmann A, et al. Gene expression profiling in MDS and AML: potential and future avenues. Leukemia. 2011;25(6):909–20.CrossRefPubMed
25.
Beurlet S, Chomienne C, Padua RA. Engineering mouse models with myelodysplastic syndrome human candidate genes; how relevant are they? Haematologica. 2013;98(1):10–22.PubMedCentralCrossRefPubMed
26.
Chau D, Ng K, Chan TS, Cheng YY, Fong B, Tam S, et al. Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9. J Hematol Oncol. 2015;8:46.PubMedCentralCrossRefPubMed
27.
Zhou T, Kinney MC, Scott LM, Zinkel SS, Rebel VI. Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research. Blood. 2015;126(9):1057–68.CrossRefPubMed
28.
Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852–7.PubMedCentralCrossRefPubMed
29.
Beurlet S, Omidvar N, Gorombei P, Krief P, Le Pogam C, Setterblad N, et al. BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells. Blood. 2013;122(16):2864–76.PubMedCentralCrossRefPubMed
30.
Le Pogam C, Krief P, Beurlet S, Soulie A, Balitrand N, Cassinat B, et al. Localization of the NRAS:BCL-2 complex determines anti-apoptotic features associated with progressive disease in myelodysplastic syndromes. Leuk Res. 2013;37(3):312–9.CrossRefPubMed
31.
Le Pogam C, Patel S, Gorombei P, Guerenne L, Krief P, Omidvar N, et al. DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies. Oncotarget. 2015;6(32):32494–508.PubMed
32.
Omidvar N, Kogan S, Beurlet S, Le Pogam C, Janin A, West R, et al. BCL-2 and mutant NRAS interact physically and functionally in a mouse model of progressive myelodysplasia. Cancer Res. 2007;67(24):11657–67.CrossRefPubMed
33.
Padua RA, Guinn BA, Al-Sabah AI, Smith M, Taylor C, Pettersson T, et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia. 1998;12(6):887–92.CrossRefPubMed
34.
Parker JE, Mufti GJ, Rasool F, Mijovic A, Devereux S, Pagliuca A. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood. 2000;96(12):3932–8.PubMed
35.
Rassool FV, Gaymes TJ, Omidvar N, Brady N, Beurlet S, Pla M, et al. Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia? Cancer Res. 2007;67(18):8762–71.CrossRefPubMed
36.
37.
Terpos E, Verrou E, Banti A, Kaloutsi V, Lazaridou A, Zervas K. Bortezomib is an effective agent for MDS/MPD syndrome with 5q- anomaly and thrombocytosis. Leuk Res. 2007;31(4):559–62.CrossRefPubMed
38.
Yue Y, Wang Y, He Y, Yang S, Chen Z, Wang Y, et al. Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. PLoS One. 2014;9(3):e90992.PubMedCentralCrossRefPubMed
39.
Benjamin DI, Cozzo A, Ji X, Roberts LS, Louie SM, Mulvihill MM, et al. Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity. Proc Natl Acad Sci U S A. 2013;110(37):14912–7.PubMedCentralCrossRefPubMed
40.
Eisenmann KM, Dykema KJ, Matheson SF, Kent NF, DeWard AD, West RA, et al. 5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics. Oncogene. 2009;28(39):3429–41.CrossRefPubMed
41.
Nyakern M, Tazzari PL, Finelli C, Bosi C, Follo MY, Grafone T, et al. Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients. Leukemia. 2006;20(2):230–8.CrossRefPubMed
42.
Franco I, Gulluni F, Campa CC, Costa C, Margaria JP, Ciraolo E, et al. PI3K class II alpha controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function. Dev Cell. 2014;28(6):647–58.PubMedCentralCrossRefPubMed
43.
Fuchs O, Provaznikova D, Kocova M, Kostecka A, Cvekova P, Neuwirtova R, et al. CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin’s lymphoma. Blood Cells Mol Dis. 2008;40(3):401–5.CrossRefPubMed
44.
Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low-/intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118(14):3765–76.CrossRefPubMed
45.
Raza A, Mehdi M, Mumtaz M, Ali F, Lascher S, Galili N. Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Cancer. 2008;113(7):1596–604.CrossRefPubMed
46.
Sood R, Makalowska I, Carpten JD, Robbins CM, Stephan DA, Connors TD, et al. The human RGL (RalGDS-like) gene: cloning, expression analysis and genomic organization. Biochim Biophys Acta. 2000;1491(1-3):285–8.CrossRefPubMed
47.
Schenkova K, Lutz J, Kopp M, Ramos S, Rivero F. MUF1/leucine-rich repeat containing 41 (LRRC41), a substrate of RhoBTB-dependent cullin 3 ubiquitin ligase complexes, is a predominantly nuclear dimeric protein. J Mol Biol. 2012;422(5):659–73.CrossRefPubMed
48.
Maeda T, Yagasaki F, Ishikawa M, Takahashi N, Bessho M. Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma that subsequently progressed to AML. Blood. 2005;105(5):2115–23.CrossRefPubMed
49.
Ross DD. Modulation of drug resistance transporters as a strategy for treating myelodysplastic syndrome. Best Pract Res Clin Haematol. 2004;17(4):641–51.CrossRefPubMed
50.
Steimle V, Durand B, Barras E, Zufferey M, Hadam MR, Mach B, et al. A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome). Genes Dev. 1995;9(9):1021–32.CrossRefPubMed
51.
Fukuda MN, Sato T, Nakayama J, Klier G, Mikami M, Aoki D, et al. Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation. Genes Dev. 1995;9(10):1199–210.CrossRefPubMed
52.
Bettermann K, Benesch M, Weis S, Haybaeck J. SUMOylation in carcinogenesis. Cancer Lett. 2012;316(2):113–25.CrossRefPubMed
53.
Pan CL, Baum PD, Gu M, Jorgensen EM, Clark SG, Garriga G. C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless. Dev Cell. 2008;14(1):132–9.PubMedCentralCrossRefPubMed
54.
Pavlaki K, Pontikoglou CG, Demetriadou A, Batsali AK, Damianaki A, Simantirakis E, et al. Impaired proliferative potential of bone marrow mesenchymal stromal cells in patients with myelodysplastic syndromes is associated with abnormal WNT signaling pathway. Stem Cells Dev. 2014;23(14):1568–81.CrossRefPubMed
55.
Bar M, Stirewalt D, Pogosova-Agadjanyan E, Wagner V, Gooley T, Abbasi N, et al. Gene expression patterns in myelodyplasia underline the role of apoptosis and differentiation in disease initiation and progression. Transl Oncogenomics. 2008;3:137–49.PubMedCentralPubMed
56.
Gal H, Amariglio N, Trakhtenbrot L, Jacob-Hirsh J, Margalit O, Avigdor A, et al. Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells. Leukemia. 2006;20(12):2147–54.CrossRefPubMed
57.
Jamieson CH, Weissman IL, Passegue E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6(6):531–3.PubMed
58.
Roversi FM, Lopes MR, Machado-Neto JA, Longhini AL, Duarte AS, Baratti MO, et al. Serine protease inhibitor kunitz-type 2 is downregulated in myelodysplastic syndromes and modulates cell-cell adhesion. Stem Cells Dev. 2014;23(10):1109–20.PubMedCentralCrossRefPubMed
59.
Movafagh S, Crook S, Vo K. Regulation of hypoxia-inducible factor-1a by reactive oxygen species: new developments in an old debate. J Cell Biochem. 2015;116(5):696–703.CrossRefPubMed
60.
Arvanitis DA, Spandidos DA. Deregulation of the G1/S phase transition in cancer and squamous intraepithelial lesions of the uterine cervix: a case control study. Oncol Rep. 2008;20(4):751–60.PubMed
61.
Saberwal G, Broderick E, Janssen I, Shetty V, Alvi S, Lisak L, et al. Involvement of cyclin D1 and E2F1 in intramedullary apoptosis in myelodysplastic syndromes. J Hematother Stem Cell Res. 2003;12(4):443–50.CrossRefPubMed
62.
Tong H, Hu C, Zhuang Z, Wang L, Jin J. Hypoxia-inducible factor-1alpha expression indicates poor prognosis in myelodysplastic syndromes. Leuk Lymphoma. 2012;53(12):2412–8.CrossRefPubMed
63.
Veraldi KL, Arhin GK, Martincic K, Chung-Ganster LH, Wilusz J, Milcarek C. hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells. Mol Cell Biol. 2001;21(4):1228–38.PubMedCentralCrossRefPubMed
64.
Boultwood J, Pellagatti A, Nikpour M, Pushkaran B, Fidler C, Cattan H, et al. The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts. PLoS One. 2008;3(4):e1970.PubMedCentralCrossRefPubMed
65.
Mazzoccoli G, De CA, Piepoli A, Vinciguerra M. The circadian clock and the hypoxic response pathway in kidney cancer. Tumour Biol. 2014;35(1):1–7.CrossRefPubMed
66.
67.
Maegawa S, Gough SM, Watanabe-Okochi N, Lu Y, Zhang N, Castoro RJ, et al. Age-related epigenetic drift in the pathogenesis of MDS and AML. Genome Res. 2014;24(4):580–91.PubMedCentralCrossRefPubMed
68.
Baratti MO, Moreira YB, Traina F, Costa FF, Verjovski-Almeida S, Olalla-Saad ST, et al. Identification of protein-coding and non-coding RNA expression profiles in CD34+ and in stromal cells in refractory anemia with ringed sideroblasts. BMC Med Genomics 2010;3:30.
69.
70.
Chapuis N, Tamburini J, Cornillet-Lefebvre P, Gillot L, Bardet V, Willems L, et al. Autocrine IGF-1/IGF-1R signaling is responsible for constitutive PI3K/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibody. Haematologica. 2010;95(3):415–23.PubMedCentralCrossRefPubMed
71.
Heredia FF, de Sousa JC, Ribeiro Junior HL, Carvalho AF, Magalhaes SM, Pinheiro RF. Proteins related to the spindle and checkpoint mitotic emphasize the different pathogenesis of hypoplastic MDS. Leuk Res. 2014;38(2):218–24.CrossRefPubMed
72.
73.
Maratheftis CI, Giannouli S, Spachidou MP, Panayotou G, Voulgarelis M. RNA interference of interferon regulatory factor-1 gene expression in THP-1 cell line leads to toll-like receptor-4 overexpression/activation as well as up-modulation of annexin-II. Neoplasia. 2007;9(12):1012–20.PubMedCentralCrossRefPubMed
74.
Mjahed H, Girodon F, Fontenay M, Garrido C. Heat shock proteins in hematopoietic malignancies. Exp Cell Res. 2012;318(15):1946–58.CrossRefPubMed
75.
Qi H, Xiao L, Lingyun W, Ying T, Yi-Zhi L, Shao-Xu Y, et al. Expression of type 1 insulin-like growth factor receptor in marrow nucleated cells in malignant hematological disorders: correlation with apoptosis. Ann Hematol. 2006;85(2):95–101.CrossRefPubMed
76.
Sukhai MA, Prabha S, Hurren R, Rutledge AC, Lee AY, Sriskanthadevan S, et al. Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors. J Clin Invest. 2013;123(1):315–28.PubMedCentralCrossRefPubMed
77.
van der Putten K, Koch B, van Someren E, Wielders J, Ter Wee P, Nagtegaal E, et al. The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease. Neuro Endocrinol Lett. 2011;32(2):148–53.PubMed
78.
Kogan SC, Ward JM, Anver MR, Berman JJ, Brayton C, Cardiff RD, et al. Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice. Blood. 2002;100(1):238–45.CrossRefPubMed
79.
Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68(5):869–77.CrossRefPubMed
80.
Fan AC, Deb-Basu D, Orban MW, Gotlib JR, Natkunam Y, O'Neill R, et al. Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens. Nat Med. 2009;15(5):566–71.PubMedCentralCrossRefPubMed
81.
de la Grange P, Dutertre M, Martin N, Auboeuf D. FAST DB: a website resource for the study of the expression regulation of human gene products. Nucleic Acids Res. 2005;33(13):4276–84.PubMedCentralCrossRefPubMed
82.
de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D. Splicing factor and exon profiling across human tissues. Nucleic Acids Res. 2010;38(9):2825–38.PubMedCentralCrossRefPubMed
83.
de la Grange P, Dutertre M, Correa M, Auboeuf D. A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants. BMC Bioinformatics. 2007;8:180.PubMedCentralCrossRefPubMed
84.
Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.CrossRef
85.
Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.PubMedCentralCrossRef
86.
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73.CrossRefPubMed
87.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.PubMedCentralCrossRefPubMed
88.
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMed
89.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51.CrossRefPubMed
Metadata
Title
GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways
Authors
Laura Guerenne
Stéphanie Beurlet
Mohamed Said
Petra Gorombei
Carole Le Pogam
Fabien Guidez
Pierre de la Grange
Nader Omidvar
Valérie Vanneaux
Ken Mills
Ghulam J Mufti
Laure Sarda-Mantel
Maria Elena Noguera
Marika Pla
Pierre Fenaux
Rose Ann Padua
Christine Chomienne
Patricia Krief
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2016
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-016-0235-8

Other articles of this Issue 1/2016

Journal of Hematology & Oncology 1/2016 Go to the issue

Research

Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors

Research

A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells

Letter to the Editor

Epidermal growth factor receptor is expressed and active in a subset of acute myeloid leukemia

Research

PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response

Research

Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-κB-mediated epithelial-mesenchymal transition

Research

The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits