Hochhaus, Andreas Gambacorti-Passerini, Carlo Abboud, Camille Gjertsen, Bjørn Tore Brümmendorf, Tim H Smith, B Douglas Ernst, Thomas Giraldo-Castellano, Pilar Olsson-Strömberg, Ulla Saussele, Susanne
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Published in
Leukemia
Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TK...
Jing, Chang-Bin Fu, Cong Prutsch, Nicole Wang, Meng He, Shuning Look, A Thomas
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Leukemia
Inactivating mutations in TET2 serve as an initiating genetic lesion in the transformation of hematopoietic stem and progenitor cells (HSPCs). Thus, effective therapy for this subset of patients would ideally include drugs that are selectively lethal in TET2-mutant HSPCs, at dosages that spare normal HSPCs. In this study, we tested 129 FDA-approved...
Gagelmann, Nico Riecken, Kristoffer Wolschke, Christine Berger, Carolina Ayuk, Francis A Fehse, Boris Kröger, Nicolaus
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Leukemia
Currently available data on chimeric antigen receptor (CAR)-T cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated multiple myeloma (MM) patients. The CAR-T field in MM is rapidly evolving with >50 currently ongoing clinical trials across all phases, different CAR-T design, or targets. Most of the CAR-T trials are pe...
Opatz, Sabrina Bamopoulos, Stefanos A Metzeler, Klaus H Herold, Tobias Ksienzyk, Bianka Bräundl, Kathrin Tschuri, Sebastian Vosberg, Sebastian Konstandin, Nikola P Wang, Christine
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Published in
Leukemia
The fusion genes CBFB/MYH11 and RUNX1/RUNX1T1 block differentiation through disruption of the core binding factor (CBF) complex and are found in 10-15% of adult de novo acute myeloid leukemia (AML) cases. This AML subtype is associated with a favorable prognosis; however, nearly half of CBF-rearranged patients cannot be cured with chemotherapy. Thi...
Kim, Ekaterina Ten Hacken, Elisa Sivina, Mariela Clarke, Astrid Thompson, Philip A Jain, Nitin Ferrajoli, Alessandra Estrov, Zeev Keating, Michael J Wierda, William G
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Leukemia
Despite major improvements in treatment outcome with novel targeted therapies, such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, chronic lymphocytic leukemia (CLL) remains incurable in the majority of patients. Activation of PI3K, NF-κB, and/or MYC has been linked to residual disease and/or resistance in ibrutinib-treated patients. Thes...
Phillips, Darren C Jin, Sha Gregory, Gareth P Zhang, Qi Xue, John Zhao, Xiaoxian Chen, Jun Tong, Yunsong Zhang, Haichao Smith, Morey
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Leukemia
MCL-1 is one of the most frequently amplified genes in cancer, facilitating tumor initiation and maintenance and enabling resistance to anti-tumorigenic agents including the BCL-2 selective inhibitor venetoclax. The expression of MCL-1 is maintained via P-TEFb-mediated transcription, where the kinase CDK9 is a critical component. Consequently, we d...
Kinstrie, Ross Horne, Gillian A Morrison, Heather Irvine, David Munje, Chinmay Castañeda, Eduardo Gómez Moka, Hothri A Dunn, Karen Cassels, Jennifer E Parry, Narissa
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Leukemia
The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed "minimal residual disease". The phenomenon of disease persistence suggests that despite targeted therapeutic approaches, B...
Verma, Divij Zanetti, Costanza Godavarthy, Parimala Sonika Kumar, Rahul Minciacchi, Valentina R Pfeiffer, Jakob Metzler, Markus Lefort, Sylvain Maguer-Satta, Véronique Nicolini, Franck E
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Published in
Leukemia
Specific and reciprocal interactions with the bone marrow microenvironment (BMM) govern the course of hematological malignancies. Matrix metalloproteinase-9 (MMP-9), secreted by leukemia cells, facilitates tumor progression via remodeling of the extracellular matrix (ECM) of the BMM. Hypothesizing that leukemias may instruct the BMM to degrade the ...
Quijada-Álamo, Miguel Hernández-Sánchez, María Alonso-Pérez, Verónica Rodríguez-Vicente, Ana E García-Tuñón, Ignacio Martín-Izquierdo, Marta Hernández-Sánchez, Jesús María Herrero, Ana B Bastida, José María San Segundo, Laura
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Published in
Leukemia
The deletion of 11q (del(11q)) invariably comprises ATM gene in chronic lymphocytic leukemia (CLL). Concomitant mutations in this gene in the remaining allele have been identified in 1/3 of CLL cases harboring del(11q), being the biallelic loss of ATM associated with adverse prognosis. Although the introduction of targeted BCR inhibition has signif...
Zeidner, Joshua F Knaus, Hanna A Zeidan, Amer M Blackford, Amanda L Montiel-Esparza, Raul Hackl, Hubert Prince, Gabrielle T Gondek, Lukasz P Ghiaur, Gabriel Showel, Margaret M
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Published in
Leukemia
An immunosuppressive microenvironment promoting leukemia cell immune escape plays an important role in the pathogenesis of AML. Through its interaction with cereblon, a substrate receptor for the E3 ubiquitin ligase complex, pomalidomide leads to selective ubiquitination of transcription factors Aiolos and Ikaros thereby promoting immune modulation...
