TITLE

Differential expression of miR-17∼92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia

AUTHOR(S)
Scherr, M; Elder, A; Battmer, K; Barzan, D; Bomken, S; Ricke-Hoch, M; Schröder, A; Venturini, L; Blair, H J; Vormoor, J; Ottmann, O; Ganser, A; Pich, A; Hilfiker-Kleiner, D; Heidenreich, O; Eder, M
PUB. DATE
March 2014
SOURCE
Leukemia (08876924);Mar2014, Vol. 28 Issue 3, p554
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17∼92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17∼92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17∼19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17∼19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17∼19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17∼92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL.
ACCESSION #
94762959

 

Related Articles

  • Extramedullary T-lymphoblastic blast crisis in chronic myelogenous leukemia: A case report of successful diagnosis and treatment. DONG-FENG ZENG; CHENG CHANG; JIE-PING LI; PEI-YAN KONG; XI ZHANG; LEI GAO // Experimental & Therapeutic Medicine;2015, Vol. 9 Issue 3, p850 

    Extramedullary T-lymphoblastic blast crisis of chronic myelogenous leukemia (CML) is uncommon and the prognosis is poor. It was usually misdiagnosed as the co-existence of T-lymphoblastic lymphoma (T-LBL) and CML. In the present study, we report a patient with CML, who developed extramedullary...

  • Requirement for CD44 in homing and engraftment of BCR-ABL–expressing leukemic stem cells. Krause, Daniela S.; Lazarides, Katherine; von Andrian, Ulrich H.; Van Etten, Richard A. // Nature Medicine;Oct2006, Vol. 12 Issue 10, p1175 

    In individuals with chronic myeloid leukemia (CML) treated by autologous hematopoietic stem cell (HSC) transplantation, malignant progenitors in the graft contribute to leukemic relapse, but the mechanisms of homing and engraftment of leukemic CML stem cells are unknown. Here we show that CD44...

  • MiR-99a may serve as a potential oncogene in pediatric myeloid leukemia. Lidan Zhang; Xiaojuan Li; Zhiyong Ke; Libin Huang; Yanni Liang; Jun Wu; Xiaoli Zhang; Yueqin Chen; Hua Zhang; Xuequn Luo // Cancer Cell International;2013, Vol. 13 Issue 1, p1 

    Background Leukemia is the most common malignant proliferative disease in children. Our previous study found that miR-99a was up-regulated in pediatric primary AML using microRNA expression profiles. Up to date, although there is a certain number of reports on microRNA expression features and...

  • Allogeneic HSCT improved outcomes for children with relapsed ALL.  // Hem/Onc Today;8/10/2013, Vol. 14 Issue 15, p20 

    The article discusses research in Germany on the benefit of allogeneic hematopoietic stem cell transplantation (HSCT) in improving the prognosis of patients with acute lymphoblastic leukemia (ALL), referencing a study by C. Eckert published in an issue of the "Journal of Clinical Oncology."

  • Synthesis of Novel Substituted 1,3-diarylpropenone Derivatives and their In Vitro Cytotoxic Activity. Ivanova, Yordanka; Momekov, Georgi; Petrov, Ognyan // Letters in Drug Design & Discovery;Jul2009, Vol. 6 Issue 5, p353 

    The synthesis of 6-[3-(3,4,5-trimethoxyphenyl)-2-propenoyl]-2(3H)-benzoxazolone, N-alkyl derivatives and their cytotoxic activity in vitro against the human cell line BV-173 (chronic myeloid leukemia in lymphoblast crisis) are described....

  • FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. Neviani, Paolo; Santhanam, Ramasamy; Oaks, Joshua J.; Eiring, Anna M.; Notari, Mario; Blaser, Bradley W.; Liu, Shujun; Trotta, Rossana; Muthusamy, Natarajan; Gambacorti-Passerini, Carlo; Druker, Brian J.; Cortes, Jorge; Marcucci, Guido; Chen, Ching-Shih; Verrills, Nicole M.; Roy, Denis C.; Caligiuri, Michael A.; Bloomfield, Clara D.; Byrd, John C.; Perrotti, Danilo // Journal of Clinical Investigation;Sep2007, Vol. 117 Issue 9, p2408 

    Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive (Ph1-positive) acute lymphocytic leukemia (ALL) are 2 fatal BCR/ABL-driven leukemias against which Abl kinase inhibitors fail to induce a long-term response. We recently reported that functional loss of...

  • Alopecia areata after HLA-identical BMT from an affected, sibling donor. Nadeem, S; Hymes, S; Kebriaei, P; Abruzzo, L; Curry, J L; Duvic, M // Bone Marrow Transplantation;Apr2014, Vol. 49 Issue 4, p592 

    Two case studies are presented such as a 48-year-old white man with chronic myelogenous leukemia (CML) and a 55-year-old white female with acute myeloid leukemia (AML). The patients have developed alopecia areata after receiving an allogeneic stem cell transplantation. It notes that alopecia...

  • Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors. The Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético). Martínez, C.; Gomez, V.; Tomás, J. F.; Parody, R.; Sureda, A.; Sanz, G.; Cañizo, C.; Díez, J. L.; Boqué, C. // Bone Marrow Transplantation;Aug2005, Vol. 36 Issue 4, p301 

    Summary:In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49...

  • The role of hematopoietic stem cell transplantation in chronic myeloid leukemia. Gratwohl, Alois; Baldomero, Helen; Passweg, Jakob // Annals of Hematology;Apr2015 Supplement, Vol. 94, p177 

    Allogeneic hematopoietic stem cell transplantation (HSCT) is currently recommended as 2nd or 3rd line therapy for patients with chronic myeloid leukemia (CML) in first chronic phase or as salvage for patients with very advanced disease. As a consequence, numbers of HSCT in chronic phase have...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics