Browsing by Author "Nazha, Aziz"

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    Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts
    (Elsevier, 2020-06-18) Zeidan, Amer M.; Boddu, Prajwal C.; Patnaik, Mrinal M.; Bewersdorf, Jan Philipp; Stahl, Maximilian; Rampal, Raajit K.; Shallis, Rory; Steensma, David P.; Savona, Michael R.; Sekeres, Mikkael A.; Roboz, Gail J.; DeAngelo, Daniel J.; Schuh, Andre C.; Padron, Eric; Zeidner, Joshua F.; Walter, Roland B.; Onida, Francesco; Fathi, Amir; DeZern, Amy; Hobbs, Gabriela; Stein, Eytan M.; Vyas, Paresh; Wei, Andrew H.; Bowen, David T.; Montesinos, Pau; Griffiths, Elizabeth A.; Verma, Amit K.; Keyzner, Alla; Bar-Natan, Michal; Navada, Shyamala C.; Kremyanskaya, Marina; Goldberg, Aaron D.; Al-Kali, Aref; Heaney, Mark L.; Nazha, Aziz; Salman, Huda; Luger, Selina; Pratz, Keith W.; Konig, Heiko; Komrokji, Rami; Deininger, Michael; Cirici, Blanca Xicoy; Bhatt, Vijaya Raj; Silverman, Lewis R.; Erba, Harry P.; Fenaux, Pierre; Platzbecker, Uwe; Santini, Valeria; Wang, Eunice S.; Tallman, Martin S.; Stone, Richard M.; Mascarenhas, John; Medicine, School of Medicine
    The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.
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    Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells
    (SpringerNature, 2017-04-25) Pan, Feng; Wingo, Thomas S.; Zhao, Zhigang; Gao, Rui; Makishima, Hideki; Qu, Guangbo; lin, Li; Yu, Miao; Ortega, Janice R.; Wang, Jiapeng; Nazha, Aziz; Chen, Li; Yao, Bing; Liu, Can; Chen, Shi; Weeks, Ophelia; Ni, Hongyu; Phillips, Brittany Lynn; Huang, Suming; Wang, Jianlong; He, Chuan; Li, Guo-Min; Radivoyevitch, Tomas; Aifantis, Iannis; Maciejewski, Jaroslaw P.; Yang, Feng-Chun; Jin, Peng; Xu, Mingjiang; Department of Pediatrics, School of Medicine
    TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2-/- mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2-/- tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies. Single-cell-targeted sequencing of wild-type and premalignant Tet2-/- Lin-c-Kit+ cells shows higher mutation frequencies in Tet2-/- cells. We further show that the increased mutational burden is particularly high at genomic sites that gained 5-hydroxymethylcytosine, where TET2 normally binds. Furthermore, TET2-mutated myeloid malignancy patients have significantly more mutational events than patients with wild-type TET2. Thus, Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated mechanism of haematological malignancy pathogenesis.