Author
Patrick A. Brown
Other affiliations: Children's Oncology Group, Johns Hopkins University School of Medicine
Bio: Patrick A. Brown is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Leukemia & Acute leukemia. The author has an hindex of 27, co-authored 115 publications receiving 2700 citations. Previous affiliations of Patrick A. Brown include Children's Oncology Group & Johns Hopkins University School of Medicine.
Papers published on a yearly basis
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TL;DR: Treatment intensity based on risk-based stratification is the cornerstone of treatment, and patients with features of more favorable disease are spared the more toxic effects of chemotherapy, whereas more aggressive regimens are reserved for those with higher-risk disease.
259 citations
University of California, San Francisco1, Broad Institute2, University of Iowa3, Johns Hopkins University4, Emory University5, Texas Tech University Health Sciences Center6, Boston Children's Hospital7, Stanford University8, University of Arkansas for Medical Sciences9, University of Utah10, University of Pittsburgh11, Washington University in St. Louis12, University of Toronto13, Cardinal Glennon Children's Hospital14, University of Minnesota15, Baylor College of Medicine16, Lehigh Valley Hospital17, Oregon Health & Science University18, University of North Carolina at Chapel Hill19, Children's National Medical Center20, Georgetown University21, University of Southern California22, Harvard University23
TL;DR: Genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML and identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription.
Abstract: Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription. Notably, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.
208 citations
TL;DR: The antileukemic activity of CEP-701 is determined, a potent and selective FLT3 inhibitor, in 8 ALL cell lines and 39 bone marrow samples obtained at diagnosis from infants and children with various subtypes of ALL, and it is concluded that it effectively suppressesFLT3-driven leukemic cell survival.
195 citations
TL;DR: It is concluded that NPMc(+) is relatively rare in childhood AML, particularly in younger children, but may contribute to risk stratification in children who lack FLT3/ITD mutations by identifying a group with superior prognosis.
194 citations
TL;DR: NPMc- AML has important prognostic significance, as NPMc+ AML, in the absence of a coexisting FLT3‐ITD mutation, is associated with a favourable outcome, and represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in N PMc+AML.
Abstract: Nucleophosmin (NPM) is a ubiquitously expressed chaperone protein that shuttles rapidly between the nucleus and cytoplasm, but predominantly resides in the nucleolus. It plays key roles in ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult acute myeloid leukaemia (AML), found in approximately 35% of all cases and up to 60% of patients with normal karyotype (NK) AML. In children, NPM1 mutations are far less frequent, occurring in 8-10% of all AML cases, and in approximately 25% of those with a NK. NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation, NPMc+ AML. NPMc+ AML is seen predominantly in patients with a NK and is essentially mutually exclusive of recurrent chromosomal translocations. Patients with NPM1 mutations are twice as likely as those who lack an NPM1 mutation to also have a FMS-like tyrosine kinase (FLT3) internal tandem duplication (ITD) mutation. NPMc+ AML is also characterized by a unique gene expression signature and microRNA signature. NPMc+ AML has important prognostic significance, as NPMc+ AML, in the absence of a coexisting FLT3-ITD mutation, is associated with a favourable outcome. NPM1 mutations have also shown great stability during disease evolution, and therefore represent a possible marker for minimal residual disease detection. Given its distinctive biologic and clinical features and its clear clinical relevance, NPMc+ AML is included as a provisional entity in the 2008 WHO classifications. There is still much to be learned about this genetic alteration, including its exact role in leukaemogenesis, how it interacts with other mutations and why it confers a more favourable prognosis. Further, it represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in NPMc+ AML.
136 citations
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29 Sep 2017
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Abstract: WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
13,835 citations
TL;DR: Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism.
Abstract: The past decade has highlighted the central role of epigenetic processes in cancer causation, progression and treatment. Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer. This view provides many surprises, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism. Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis. The enzymatic processes that control the epigenome present new opportunities for deriving therapeutic strategies designed to reverse transcriptional abnormalities that are inherent to the cancer epigenome.
2,483 citations
TL;DR: This review considers recent advances in the treatment of ALL, emphasizing issues that need to be addressed if treatment outcome is to improve further.
Abstract: Although the overall cure rate of acute lymphoblastic leukemia (ALL) in children is about 80 percent, affected adults fare less well. This review considers recent advances in the treatment of ALL, emphasizing issues that need to be addressed if treatment outcome is to improve further.
1,780 citations
TL;DR: It remains uncertain whether the stem cell model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells.
1,043 citations