Genomes and Genes
leukemic gene expression regulation
Summary: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.
- Ploner C, Rainer J, Lobenwein S, Geley S, Kofler R. Repression of the BH3-only molecule PMAIP1/Noxa impairs glucocorticoid sensitivity of acute lymphoblastic leukemia cells. Apoptosis. 2009;14:821-8 pubmed publisher..Interfering with the anti-apoptotic component of the GC response might contribute to improved therapeutic approaches and circumvention of resistance to this therapy. ..
- Rogers S, Zhao Y, Jiang X, Eaves C, Mager D, Rouhi A. Expression of the leukemic prognostic marker CD7 is linked to epigenetic modifications in chronic myeloid leukemia. Mol Cancer. 2010;9:41 pubmed publisher..These findings indicate a link between epigenetic modifications and CD7 expression in primitive CML cells. ..
- Hulleman E, Kazemier K, Holleman A, VanderWeele D, Rudin C, Broekhuis M, et al. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells. Blood. 2009;113:2014-21 pubmed publisher..Together, these findings indicate the importance of the glycolytic pathway in glucocorticoid resistance in ALL and suggest that targeting glycolysis is a viable strategy for modulating prednisolone resistance in ALL. ..
- Bomben R, Dal Bo M, Capello D, Forconi F, Maffei R, Laurenti L, et al. Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study. Br J Haematol. 2009;144:492-506 pubmed publisher..Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR. ..
- Lugthart S, van Drunen E, van Norden Y, van Hoven A, Erpelinck C, Valk P, et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood. 2008;111:4329-37 pubmed publisher..001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML. ..
- Bueno M, Perez de Castro I, Gómez de Cedrón M, Santos J, Calin G, Cigudosa J, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13:496-506 pubmed publisher..Thus, miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies. ..
- Jongen Lavrencic M, Sun S, Dijkstra M, Valk P, Lowenberg B. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood. 2008;111:5078-85 pubmed publisher..MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML. ..
- Haas K, Kundi M, Sperr W, Esterbauer H, Ludwig W, Ratei R, et al. Expression and prognostic significance of different mRNA 5'-end variants of the oncogene EVI1 in 266 patients with de novo AML: EVI1 and MDS1/EVI1 overexpression both predict short remission duration. Genes Chromosomes Cancer. 2008;47:288-98 pubmed publisher..This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. ..
- Deaglio S, Aydin S, Vaisitti T, Bergui L, Malavasi F. CD38 at the junction between prognostic marker and therapeutic target. Trends Mol Med. 2008;14:210-8 pubmed publisher..The use of reagents specifically blocking the molecule might provide a new approach for interfering with deleterious growth circuits, therefore increasing the susceptibility of leukemic cells to conventional chemotherapy. ..
- Hess C, Errami A, Berkhof J, Denkers F, Ossenkoppele G, Nygren A, et al. Concurrent methylation of promoters from tumor associated genes predicts outcome in acute myeloid leukemia. Leuk Lymphoma. 2008;49:1132-41 pubmed publisher..In addition, ESR1 methylation may reflect a biological pathway that leads to hypermethylation of multiple genes, which is reflected by methylation of IGSF4 and/or CDKN2B/p15. ..
- Li H, Liu L, Guo L, Zhang J, Du W, Li X, et al. HERG K+ channel expression in CD34+/CD38-/CD123(high) cells and primary leukemia cells and analysis of its regulation in leukemia cells. Int J Hematol. 2008;87:387-392 pubmed publisher..These data provide evidence for the oncogenic potential of HERG K+ channels and it may be a novel, potential pharmacological target for leukemia therapy in the future. ..
- White D, Dang P, Engler J, Frede A, Zrim S, Osborn M, et al. Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib. J Clin Oncol. 2010;28:2761-7 pubmed publisher..Early dose-intensity may reduce the negative prognostic impact of low OA. We propose that OA could be used to individualize dosage strategies for patients with CML to maximize molecular response and optimize long-term outcome. ..
- Polakova K, Bandzuchova E, Sabty F, Mistrik M, Demitrovicova L, Russ G. Activation of HLA-G expression by 5-aza-2 - deoxycytidine in malignant hematopoetic cells isolated from leukemia patients. Neoplasma. 2009;56:514-20 pubmed..We detected HLA-G expression in untreated cells from some patients. Nevertheless treatment with 5-aza-2 - deoxycytidine enhanced HLA-G transcription and concomitantly HLA-G protein synthesis in some leukemia cells. ..
- Hyde R, Kamikubo Y, Anderson S, Kirby M, Alemu L, Zhao L, et al. Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11. Blood. 2010;115:1433-43 pubmed publisher..These results suggest that Cbfb/Runx1 repression-independent activities contribute to leukemogenesis by Cbfb-MYH11. ..
- Schwieger M, Schuler A, Forster M, Engelmann A, Arnold M, Delwel R, et al. Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C. Blood. 2009;114:2476-88 pubmed publisher..Thus, MEF2C up-regulation may be responsible for the aggressive nature of this leukemia subtype. ..
- Chou W, Hou H, Chen C, Tang J, Yao M, Tsay W, et al. Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. Blood. 2010;115:2749-54 pubmed publisher..We conclude that IDH1 is associated with distinct clinical and biologic characteristics and seems to be very stable during disease evolution. ..
- Bruchova Votavova H, Yoon D, Prchal J. miR-451 enhances erythroid differentiation in K562 cells. Leuk Lymphoma. 2010;51:686-93 pubmed publisher..These data support the concept that aberrant expression of miRNAs may contribute to abnormal erythropoiesis such as that of PV. ..
- Zhara M, Mourad H, Farouk G, Elbatch M, Ezzat S, Sami W. Molecular detection of survivin expression, antiapoptotic gene, and other prognostic markers, how they are correlated and how it could be of prognostic value in chronic myeloid leukemia patient. Egypt J Immunol. 2007;14:51-62 pubmed..50). In conclusion, survivin is expressed in most cases of CML patients and its over expression is associated with bad prognosis. ..
- Tsukahara F, Maru Y. Bag1 directly routes immature BCR-ABL for proteasomal degradation. Blood. 2010;116:3582-92 pubmed publisher..Bag1 may direct CHIP/Hsc70-regulated protein triage decisions on BCR-ABL immediately after translation to the degradation pathway. ..
- Yustein J, Liu Y, Gao P, Jie C, Le A, Vuica Ross M, et al. Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model. Proc Natl Acad Sci U S A. 2010;107:3534-9 pubmed publisher..Furthermore, the expression of Jagged2 in P493-6 tumors often overlapped with regions of hypoxia. These observations suggest that Notch signaling downstream of Myc enables cells to adapt in the tumor hypoxic microenvironment. ..
- Thiel A, Blessington P, Zou T, Feather D, Wu X, Yan J, et al. MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele. Cancer Cell. 2010;17:148-59 pubmed publisher..These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis. ..
- Nowak N, Sait S, Zeidan A, Deeb G, Gaile D, Liu S, et al. Recurrent deletion of 9q34 in adult normal karyotype precursor B-cell acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2010;199:15-20 pubmed publisher..This aberration has not been described before in adult NK B-ALL. Larger number of samples is warranted to determine the prognostic significance of this cryptic deletion. ..
- Hughes T, Saglio G, Branford S, Soverini S, Kim D, Muller M, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol. 2009;27:4204-10 pubmed publisher..However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib. ..
- Teiten M, Eifes S, Reuter S, Duvoix A, Dicato M, Diederich M. Gene expression profiling related to anti-inflammatory properties of curcumin in K562 leukemia cells. Ann N Y Acad Sci. 2009;1171:391-8 pubmed publisher..This study also indicated that the upregulation of the heat shock family genes is highly implicated in the anti-inflammatory effect of curcumin. ..
- Li Z, Luo R, Mi S, Sun M, Chen P, Bao J, et al. Consistent deregulation of gene expression between human and murine MLL rearrangement leukemias. Cancer Res. 2009;69:1109-16 pubmed publisher..The identification and validation of consistent changes of gene expression in human and murine MLL rearrangement leukemias provide important insights into the genetic base for MLL-associated leukemogenesis. ..
- Zhang Q, Mao J, Liu P, Huang Q, Lu J, Xie Y, et al. A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A. 2009;106:3378-83 pubmed publisher..Thus, these results suggest potential clinical benefits of IM/AS combination therapy for human CML. ..
- Gery S, Gueller S, Nowak V, Sohn J, Hofmann W, Koeffler H. Expression of the adaptor protein Lnk in leukemia cells. Exp Hematol. 2009;37:585-592.e2 pubmed publisher..Although how leukemic cells overcome the antiproliferative effects of Lnk is not yet clear, our data highlight the multifaceted role negative feedback mechanisms play in malignant transformation. ..
- Nishioka C, Ikezoe T, Yang J, Yokoyama A. Inhibition of MEK signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells. Apoptosis. 2009;14:1108-20 pubmed publisher..Taken together, concomitant administration of AraC and the inhibitor of MEK/ERK signaling may be useful for treatment of individuals with AML. ..
- Demers M, Couillard J, Giglia Mari G, Magnaldo T, St Pierre Y. Increased galectin-7 gene expression in lymphoma cells is under the control of DNA methylation. Biochem Biophys Res Commun. 2009;387:425-9 pubmed publisher..Collectively, our data suggest that abnormal expression of galectin-7 in lymphoma cells is not dependent on p53, but is rather associated with DNA hypomethylation. ..
- Zenz T, Häbe S, Denzel T, Mohr J, Winkler D, Bühler A, et al. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood. 2009;114:2589-97 pubmed publisher..Alemtuzumab is effective irrespective of genetic high-risk subgroups with TP53 mutations. These clinical trials are registered at www.clinicaltrials.gov as #NCT00274976. ..
- Bellon M, Lepelletier Y, Hermine O, Nicot C. Deregulation of microRNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia. Blood. 2009;113:4914-7 pubmed publisher..Specifically, miR-150 and miR-223 were up-regulated in ATL patients but consistently down-regulated in HTLV-I cell lines, suggesting that ATL cells and in vitro-established cells are derived from distinct cellular populations. ..
- Sada E, Abe Y, Ohba R, Tachikawa Y, Nagasawa E, Shiratsuchi M, et al. Vitamin K2 modulates differentiation and apoptosis of both myeloid and erythroid lineages. Eur J Haematol. 2010;85:538-48 pubmed publisher..Although the detailed mechanism of VK2's effect on differentiation or apoptosis of hematopoietic progenitors remains unknown, the effect of VK2 therapy in patients with MDS could be partly explained by these mechanisms. ..
- Tang C, Shi X, Wang W, Zhou D, Tu J, Xie X, et al. Global analysis of in vivo EGR1-binding sites in erythroleukemia cell using chromatin immunoprecipitation and massively parallel sequencing. Electrophoresis. 2010;31:2936-43 pubmed publisher..This whole genome study on the EGR1 targets may provide a better understanding of the EGR1 regulated genes and the downstream pathway in megakaryocyte differentiation. ..
- Becker H, Marcucci G, Maharry K, Radmacher M, Mrozek K, Margeson D, et al. Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood. 2010;116:788-92 pubmed publisher..Our results indicate that WT1mut CN-AML represents a distinct entity with poor treatment response across age groups. This study has been registered at www.clinicaltrials.gov as #NCT00900224...
- Meani N, Alcalay M. Role of nucleophosmin in acute myeloid leukemia. Expert Rev Anticancer Ther. 2009;9:1283-94 pubmed publisher..In this review we summarize recent discoveries concerning NPM function, and discuss their possible impact on the pathogenesis of acute myeloid leukemias with mutated NPM1. ..
- Oki Y, Issa J. Epigenetic mechanisms in AML - a target for therapy. Cancer Treat Res. 2010;145:19-40 pubmed publisher..Recent clinical studies have shown the relative safety and efficacy of such epigenetic therapies. ..
- Tavolaro S, Chiaretti S, Messina M, Peragine N, del Giudice I, Marinelli M, et al. Gene expression profile of protein kinases reveals a distinctive signature in chronic lymphocytic leukemia and in vitro experiments support a role of second generation protein kinase inhibitors. Leuk Res. 2010;34:733-41 pubmed publisher..These findings suggest that treatment with second generation tyrosine kinase (TK) inhibitors may represent an attractive therapeutic strategy for CLL patients. ..
- Li L, Zhang R, Fang Z, Chen J, Zhu Z. Suppression of vascular endothelial growth factor (VEGF) expression by targeting the Bcr-Abl oncogene and protein tyrosine kinase activity in Bcr-Abl-positive leukaemia cells. J Int Med Res. 2009;37:426-37 pubmed..The combined application of Bcr-Abl-targeting siRNAs and imatinib may provide a potent novel therapeutic approach for chronic myeloid leukaemia. ..
- Gleixner K, Ferenc V, Peter B, Gruze A, Meyer R, Hadzijusufovic E, et al. Polo-like kinase 1 (Plk1) as a novel drug target in chronic myeloid leukemia: overriding imatinib resistance with the Plk1 inhibitor BI 2536. Cancer Res. 2010;70:1513-23 pubmed publisher..In conclusion, Plk1 is expressed in CML cells and may represent a novel, interesting target in imatinib-sensitive and imatinib-resistant CML. ..
- Matsumoto T, Jimi S, Hara S, Takamatsu Y, Suzumiya J, Tamura K. Am80 inhibits stromal cell-derived factor-1-induced chemotaxis in T-cell acute lymphoblastic leukemia cells. Leuk Lymphoma. 2010;51:507-14 pubmed publisher..Am80 may be an effective drug to inhibit the extramedullary infiltration of T-ALL cells. ..
- Wray J, Williamson E, Sheema S, Lee S, Libby E, Willman C, et al. Metnase mediates chromosome decatenation in acute leukemia cells. Blood. 2009;114:1852-8 pubmed publisher..Thus, Metnase expression levels may predict AML resistance to Topo IIalpha inhibitors, and Metnase is a potential therapeutic target for small molecule interference. ..
- Falini B, Macijewski K, Weiss T, Bacher U, Schnittger S, Kern W, et al. Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood. 2010;115:3776-86 pubmed publisher..Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML represents one disease entity clearly distinct from AML with MRCs. ..
- Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary M. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell. 2010;17:198-212 pubmed publisher..Thus, AEP recruitment is an integral part of both physiological and pathological MLL-dependent transcriptional pathways. Bypass of its normal recruitment mechanisms is the strategy most frequently used by MLL oncoproteins. ..
- Park M, Taki T, Oda M, Watanabe T, Yumura Yagi K, Kobayashi R, et al. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma. Br J Haematol. 2009;145:198-206 pubmed publisher..9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively). ..
- Debatin K. Growth control of normal and malignant lymphocytes--cell death research from basic concepts to signal pathways and translation into the clinic. Klin Padiatr. 2009;221:332-8 pubmed publisher..In this review, an overview of the developments in the field from basic discoveries to the recent clinical trials is given. ..
- Whitman S, Maharry K, Radmacher M, Becker H, Mrozek K, Margeson D, et al. FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood. 2010;116:3622-6 pubmed publisher..FLT3-ITD identifies older CN-AML patients with molecular high risk and is associated with gene- and microRNA-expression signatures that provide biologic insights for novel therapeutic approaches. ..
- Krivtsov A, Feng Z, Lemieux M, Faber J, Vempati S, Sinha A, et al. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008;14:355-68 pubmed publisher..We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression. ..
- Bühler A, Zenz T, Stilgenbauer S. Immunoglobulin heavy chain variable gene usage and (super)-antigen drive in chronic lymphocytic leukemia. Clin Cancer Res. 2010;16:373-5 pubmed publisher..The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups. ..