Full Text Journal Articles by
Author Junia V Melo


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A kinase-independent role for CDK8 in BCR-ABL1+ leukemia.

Ingeborg Menzl, Tinghu Zhang, Angelika Berger-Becvar, Reinhard Grausenburger, Gerwin Heller, Michaela Prchal-Murphy, Leo Edlinger, Vanessa M Knab, Iris Z Uras, Eva Grundschober, Karin Bauer, Mareike Roth, Anna Skucha, Yao Liu, John M Hatcher, Yanke Liang, Nicholas P Kwiatkowski, Daniela Fux, Andrea Hoelbl-Kovacic, Stefan Kubicek, Junia V Melo, Peter Valent, Thomas Weichhart, Florian Grebien, Johannes Zuber, Nathanael S Gray, Veronika Sexl,

Cyclin-dependent kinases (CDKs) are frequently deregulated in cancer and represent promising drug targets. We provide evidence that CDK8 has a key role in B-ALL. Loss of CDK8 in leukemia mouse models significantly enhances disease latency and prevents disease maintenance. Loss of CDK8 is associated with pronounced transcriptional changes, whereas inhibiting ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):4741]

Cited: 0 times

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Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition.

Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, Emma Shanks, Bruno Calabretta, Tessa L Holyoake, G Vignir Helgason,

Background:Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, ... Read more >>

J. Natl. Cancer Inst. (Journal of the National Cancer Institute)
[2018, 110(5):467-478]

Cited: 11 times

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Phenotyping and Target Expression Profiling of CD34+/CD38- and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia.

Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent,

Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+/CD38- LSCs in patients ... Read more >>

Neoplasia (Neoplasia (New York, N.Y.))
[2018, 20(6):632-642]

Cited: 6 times

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The pan-BCL-2-blocker obatoclax (GX15-070) and the PI3-kinase/mTOR-inhibitor BEZ235 produce cooperative growth-inhibitory effects in ALL cells.

Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent,

Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the ... Read more >>

Oncotarget (Oncotarget)
[2017, 8(40):67709-67722]

Cited: 4 times

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Pro-survival role of protein kinase C epsilon in Philadelphia chromosome positive acute leukemia.

To Ha Loi, Pei Dai, Stephen Carlin, Junia V Melo, David D F Ma,

Durable responses to imatinib monotherapy are rarely seen in aggressive forms of Philadelphia chromosome positive (Ph+) leukemias. To investigate the possible cause of treatment failure we examined the role of protein kinase C epsilon (PKCE), an oncogene highly implicated in the development of solid tumors and resistance to chemotherapy. We ... Read more >>

Leuk. Lymphoma (Leukemia & lymphoma)
[2016, 57(2):411-418]

Cited: 0 times

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Natural course and biology of CML.

Bradley Chereda, Junia V Melo,

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder arising in the haemopoietic stem cell (HSC) compartment. This disease is characterised by a reciprocal t(9;22) chromosomal translocation, resulting in the formation of the Philadelphia (Ph) chromosome containing the BCR-ABL1 gene. As such, diagnosis and monitoring of disease involves detection of BCR-ABL1. ... Read more >>

Ann. Hematol. (Annals of hematology)
[2015, 94 Suppl 2:S107-21]

Cited: 45 times

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Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia.

Sabine Cerny-Reiterer, Renata A Meyer, Harald Herrmann, Barbara Peter, Karoline V Gleixner, Gabriele Stefanzl, Emir Hadzijusufovic, Winfried F Pickl, Wolfgang R Sperr, Junia V Melo, Hiroshi Maeda, Ulrich Jäger, Peter Valent,

Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph+ chronic myeloid leukemia. We here report that primary cells and cell lines derived from patients with acute lymphoblastic ... Read more >>

Oncotarget (Oncotarget)
[2014, 5(5):1198-1211]

Cited: 11 times

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A target-disease network model of second-generation BCR-ABL inhibitor action in Ph+ ALL.

Uwe Rix, Jacques Colinge, Katharina Blatt, Manuela Gridling, Lily L Remsing Rix, Katja Parapatics, Sabine Cerny-Reiterer, Thomas R Burkard, Ulrich Jäger, Junia V Melo, Keiryn L Bennett, Peter Valent, Giulio Superti-Furga,

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is in part driven by the tyrosine kinase bcr-abl, but imatinib does not produce long-term remission. Therefore, second-generation ABL inhibitors are currently in clinical investigation. Considering different target specificities and the pronounced genetic heterogeneity of Ph+ ALL, which contributes to the aggressiveness of ... Read more >>

PLoS ONE (PloS one)
[2013, 8(10):e77155]

Cited: 6 times

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Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study.

David M Ross, Susan Branford, John F Seymour, Anthony P Schwarer, Christopher Arthur, David T Yeung, Phuong Dang, Jarrad M Goyne, Cassandra Slader, Robin J Filshie, Anthony K Mills, Junia V Melo, Deborah L White, Andrew P Grigg, Timothy P Hughes,

Most patients with chronic myeloid leukemia (CML) treated with imatinib will relapse if treatment is withdrawn. We conducted a prospective clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease (UMRD) by conventional quantitative polymerase chain reaction (PCR) on imatinib for at least ... Read more >>

Blood (Blood)
[2013, 122(4):515-522]

Cited: 309 times

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Cancer stem cell definitions and terminology: the devil is in the details.

Peter Valent, Dominique Bonnet, Ruggero De Maria, Tsvee Lapidot, Mhairi Copland, Junia V Melo, Christine Chomienne, Fumihiko Ishikawa, Jan Jacob Schuringa, Giorgio Stassi, Brian Huntly, Harald Herrmann, Jean Soulier, Alexander Roesch, Gerrit Jan Schuurhuis, Stefan Wöhrer, Michel Arock, Johannes Zuber, Sabine Cerny-Reiterer, Hans E Johnsen, Michael Andreeff, Connie Eaves,

The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and ... Read more >>

Nat. Rev. Cancer (Nature reviews. Cancer)
[2012, 12(11):767-775]

Cited: 282 times

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Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells.

Daniel B Lipka, Marie-Christine Wagner, Marek Dziadosz, Tina Schnöder, Florian Heidel, Mirle Schemionek, Junia V Melo, Thomas Kindler, Carsten Müller-Tidow, Steffen Koschmieder, Thomas Fischer,

Clinical development of imatinib in CML established continuous target inhibition as a paradigm for successful tyrosine kinase inhibitor (TKI) therapy. However, recent reports suggested that transient potent target inhibition of BCR-ABL by high-dose TKI (HD-TKI) pulse-exposure is sufficient to irreversibly commit cells to apoptosis. Here, we report a novel mechanism ... Read more >>

PLoS ONE (PloS one)
[2012, 7(7):e40853]

Cited: 15 times

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BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia.

Swagata Roy, Heather G Jørgensen, Poornima Roy, Mohamed Abed El Baky, Junia V Melo, Gordon Strathdee, Tessa L Holyoake, Chris Bartholomew,

MECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony-forming cells by 34% and moderately reduces BCR-ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in ... Read more >>

Br. J. Haematol. (British journal of haematology)
[2012, 157(4):446-456]

Cited: 7 times

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Imatinib mesylate at therapeutic doses has no impact on folliculogenesis or spermatogenesis in a leukaemic mouse model.

Beate Schultheis, Bart A Nijmeijer, H Yin, Roger G Gosden, Junia V Melo,

Imatinib should be avoided in women planning to become pregnant or during pregnancy, due to a higher risk of congenital malformations. However, it is not known whether imatinib affects future potential for fertility. Here we analysed ovaries and testes from adult mice receiving imatinib, focusing on testicular and ovarian functions. ... Read more >>

Leuk. Res. (Leukemia research)
[2012, 36(3):271-274]

Cited: 25 times

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Chronic myeloid leukemia: the basis of treatment for tomorrow.

Angelo M Carella, John M Goldman, Giovanni Martinelli, Junia V Melo, Danilo Perrotti,

Haematologica (Haematologica)
[2011, 96(12):1737-1739]

Cited: 3 times

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Rapid automated detection of ABL kinase domain mutations in imatinib-resistant patients.

Ruriko Tanaka, Shinya Kimura, Eishi Ashihara, Mariko Yoshimura, Naoto Takahashi, Hisashi Wakita, Kuniaki Itoh, Kaichi Nishiwaki, Kenshi Suzuki, Rina Nagao, Hisayuki Yao, Yoshihiro Hayashi, Sakiko Satake, Hideyo Hirai, Ken-Ichi Sawada, Oliver G Ottmann, Junia V Melo, Taira Maekawa,

ABL tyrosine kinase inhibitor (TKI), imatinib is used for BCR-ABL(+) leukemias. We developed an automatic method utilizing guanine-quenching probes (QP) to detect 17 kinds of mutations frequently observed in imatinib-resistance. Results were obtained from 100μL of whole blood within 90min by this method. Detected mutations were almost identical between QP ... Read more >>

Cancer Lett. (Cancer letters)
[2011, 312(2):228-234]

Cited: 6 times

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Clonal and lineage analysis of somatic DNMT3A and JAK2 mutations in a chronic phase polycythemia vera patient.

Nisha Rao, Carolyn M Butcher, Ian D Lewis, David M Ross, Junia V Melo, Hamish S Scott, Peter G Bardy, Richard J D'Andrea,

Br. J. Haematol. (British journal of haematology)
[2012, 156(2):268-270]

Cited: 5 times

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SHP-1 expression accounts for resistance to imatinib treatment in Philadelphia chromosome-positive cells derived from patients with chronic myeloid leukemia.

Nicola Esposito, Irene Colavita, Concetta Quintarelli, Agostino Rodeo Sica, Anna Lucia Peluso, Luigia Luciano, Marco Picardi, Luigi Del Vecchio, Tonia Buonomo, Timothy P Hughes, Deborah White, Jerald P Radich, Domenico Russo, Susan Branford, Giuseppe Saglio, Junia V Melo, Rosanna Martinelli, Margherita Ruoppolo, Thea Kalebic, Giovanni Martinelli, Fabrizio Pane,

We prove that the SH2-containing tyrosine phosphatase 1 (SHP-1) plays a prominent role as resistance determinant of imatinib (IMA) treatment response in chronic myelogenous leukemia cell lines (sensitive/KCL22-S and resistant/KCL22-R). Indeed, SHP-1 expression is significantly lower in resistant than in sensitive cell line, in which coimmunoprecipitation analysis shows the interaction ... Read more >>

Blood (Blood)
[2011, 118(13):3634-3644]

Cited: 28 times

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Mechanisms of resistance to BCR-ABL kinase inhibitors.

Joana M Diamond, Junia V Melo,

Since the introduction of imatinib mesylate (IM) for the treatment of chronic myeloid leukemia (CML), impressive clinical responses have been observed in the majority of patients in chronic phase. However, not all patients experience an optimal response to IM or even to the more potent, second-generation tyrosine kinase inhibitors (TKIs). ... Read more >>

Leuk. Lymphoma (Leukemia & lymphoma)
[2011, 52 Suppl 1:12-22]

Cited: 27 times

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RUNX1 mutations are rare in chronic phase polycythaemia vera.

Carolyn M Butcher, Petra J Neufing, Lena Eriksson, Catherine L Carmichael, Ella J Wilkins, Junia V Melo, Ian D Lewis, Peter G Bardy, Hamish S Scott, Richard J D'Andrea,

Br. J. Haematol. (British journal of haematology)
[2011, 153(5):672-675]

Cited: 1 time

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Minimal residual disease and discontinuation of therapy in chronic myeloid leukemia: can we aim at a cure?

Junia V Melo, David M Ross,

Patients with chronic myeloid leukemia (CML) who have achieved a complete molecular response (CMR) defined by no detectable BCR-ABL mRNA on imatinib (IM) treatment often ask whether it is necessary for treatment to continue. We now know that approximately 40% of patients with a stable CMR for at least 2 ... Read more >>

Hematology Am Soc Hematol Educ Program (Hematology. American Society of Hematology. Education Program)
[2011, 2011:136-142]

Cited: 13 times

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Gaining insights into the Bcr-Abl activity-independent mechanisms of resistance to imatinib mesylate in KCL22 cells: a comparative proteomic approach.

Irene Colavita, Nicola Esposito, Rosanna Martinelli, Francesca Catanzano, Junia V Melo, Fabrizio Pane, Margherita Ruoppolo, Francesco Salvatore,

Imatinib mesylate is a potent inhibitor of Bcr-Abl tyrosine kinase, an oncoprotein that plays a key role in the development of chronic myeloid leukemia. Consequently, imatinib is used as front-line therapy for this disease. A major concern in imatinib treatment is the emergence of resistance to the drug. Here we ... Read more >>

Biochim. Biophys. Acta (Biochimica et biophysica acta)
[2010, 1804(10):1974-1987]

Cited: 10 times

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Wrapping BCR-ABL: it's in the bag.

Junia V Melo, Duncan R Hewett,

Leukemia, with its origin in a specific genetic abnormality, will only arise if the cell properly folds and processes the oncogenic protein encoded by the mutant gene. In this issue of Blood, Tsukahara and Maru describe a set of proteins that control the processing of the nascent BCR-ABL oncoprotein, providing ... Read more >>

Blood (Blood)
[2010, 116(18):3382-3383]

Cited: 0 times

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A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib.

Shannon K McWeeney, Lucy C Pemberton, Marc M Loriaux, Kristina Vartanian, Stephanie G Willis, Gregory Yochum, Beth Wilmot, Yaron Turpaz, Raji Pillai, Brian J Druker, Jennifer L Snead, Mary MacPartlin, Stephen G O'Brien, Junia V Melo, Thoralf Lange, Christina A Harrington, Michael W N Deininger,

In chronic-phase chronic myeloid leukemia (CML) patients, the lack of a major cytogenetic response (< 36% Ph(+) metaphases) to imatinib within 12 months indicates failure and mandates a change of therapy. To identify biomarkers predictive of imatinib failure, we performed gene expression array profiling of CD34(+) cells from 2 independent ... Read more >>

Blood (Blood)
[2010, 115(2):315-325]

Cited: 69 times

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Metabolic characteristics of imatinib resistance in chronic myeloid leukaemia cells.

Jelena Klawitter, Douglas J Kominsky, Jaimi L Brown, Jost Klawitter, Uwe Christians, Dieter Leibfritz, Junia V Melo, S Gail Eckhardt, Natalie J Serkova,

Early detection of resistance development is crucial for imatinib-based treatment in chronic myeloid leukaemia (CML) patients. We aimed to distinguish metabolic markers of cell resistance to imatinib.Two human imatinib-sensitive CML cell lines: LAMA84-s and K562-s, and their resistant counterparts: LAMA84-r and K562-r (both resistant to 1 microM imatinib), and K562-R ... Read more >>

Br. J. Pharmacol. (British journal of pharmacology)
[2009, 158(2):588-600]

Cited: 39 times

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In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib.

Manuel Sobrinho-Simões, Vicki Wilczek, Joannah Score, Nicholas C P Cross, Jane F Apperley, Junia V Melo,

It is not clear if absence of BCR-ABL transcripts--complete molecular response (CMR)--is synonymous with, or required for, cure of chronic myeloid leukemia (CML). Some patients achieve CMR with imatinib (IM), but most relapse shortly after treatment discontinuation. Furthermore, most patients in long-term remission (LTR) post-stem cell transplantation (SCT) are considered ... Read more >>

Blood (Blood)
[2010, 116(8):1329-1335]

Cited: 47 times

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