Browsing by Author "Walker, Brian"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies
    (Taylor & Francis, 2021) Bisht, Kamlesh; Walker, Brian; Kumar, Shaji K.; Spicka, Ivan; Moreau, Philippe; Martin, Tom; Costa, Luciano J.; Richter, Joshua; Fukao, Taro; Macé, Sandrine; van de Velde, Helgi; Medicine, School of Medicine
    Multiple myeloma (MM) remains an incurable disease with a median overall survival of approximately 5 years. Gain or amplification of 1q21 (1q21+) occurs in around 40% of patients with MM and generally portends a poor prognosis. Patients with MM who harbor 1q21+ are at increased risk of drug resistance, disease progression, and death. New pharmacotherapies with novel modes of action are required to overcome the negative prognostic impact of 1q21+. Areas covered: This review discusses the detection, biology, prognosis, and therapeutic targeting of 1q21+ in newly diagnosed and relapsed MM. Patients with MM and 1q21+ tend to present with higher tumor burden, greater end-organ damage, and more co-occurring high-risk cytogenetic abnormalities than patients without 1q21+. The chromosomal rearrangements associated with 1q21+ result in dysregulation of genes involved in oncogenesis. Identification and characterization of the 1q21+ molecular targets are needed to inform on prognosis and treatment strategy. Clinical trial data are emerging that addition of isatuximab to combination therapies may improve outcomes in patients with 1q21+ MM. Expert opinion: In the next 5 years, the results of ongoing research and trials are likely to focus on the therapeutic impact and treatment decisions associated with 1q21+ in MM.
  • Thumbnail Image
    Item
    Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities
    (Springer Nature, 2021-03-25) Oben, Bénedith; Froyen, Guy; Maclachlan, Kylee H.; Leongamornlert, Daniel; Abascal, Federico; Zheng-Lin, Binbin; Yellapantula, Venkata; Derkach, Andriy; Geerdens, Ellen; Diamond, Benjamin T.; Arijs, Ingrid; Maes, Brigitte; Vanhees, Kimberly; Hultcrantz, Malin; Manasanch, Elisabet E.; Kazandjian, Dickran; Lesokhin, Alexander; Dogan, Ahmet; Zhang, Yanming; Mikulasova, Aneta; Walker, Brian; Morgan, Gareth; Campbell, Peter J.; Landgren, Ola; Rummens, Jean-Luc; Bolli, Niccolò; Maura, Francesco; Medicine, School of Medicine
    Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.