Core A is responsible for the identification and enrollment of every adult patient referred to the Siteman Cancer Center with newly diagnosed and relapsed acute myeloid leukemia (AML) and Myelodysplastic Syndrome (MDS). The clinical and pathologic material from these patients are entered into databases that are required for the execution of this program project. Additionally, clinical, pathologic and therapeutic information are essential for determining the clinical relevance of a newly identified genetic mutation. The Clinical Database Core (Core A) was established in 2002 to serve as a platform for the investigation of genetic mutations associated with the pathogenesis of MDS and acute myeloid leukemia, and has two Specific Aims, as follows:
Specific Aim 1 : We will prospectively identify and enroll on study all patients with newly diagnosed or relapsed AML and MDS referred to Washington University Siteman Cancer Center. Since its establishment, Core A has been responsible for banking tissue from 167 MDS and 387 AML patients (-98% accrual) according to an IRB approved Tissue Acquisition protocol. From these 554 patients, bone marrow was collected from 515 (93%), blood from 517 (93%), serum from 455 (82%), skin from 495 (89%), and oral mucosa cells from 376 (68%), as of 4/1/07. Additional tumor specimens were collected from 28 of the AML patients at the time of relapse/progression;additional tumor specimens were collected from 13 of the MDS patients at the time of progression to AML. Since January of 2007, 43 patients have been reconsented so that their samples can be used for the whole genome resequencing studies of Project 1.
Specific Aim 2 : We will establish a comprehensive clinical leukemia database that will capture epidemiological data, disease-related characteristics, prognostic factors, therapeutic information, and outcomes from all newly diagnosed and relapsed AML and MDS patients referred to Siteman Cancer Center. Along with genomic data obtained on specimens collected from these patients and stored in the Specimen Acquisition and Expression Profiling Core (Core B), this comprehensive database will provide the Project 2 and the Biostatistics Core (Core C) with critical elements to test and validate the prognostic significance of any given mutation. Comprehensive disease-specific and outcomes data has been compiled on every patient in a de-identified database. This effort has facilitated the compilation of a well defined and uniform set of 94 samples from patients with de novo AML (primarily MO-M4) with >30% blasts, <2 clonal cytogenetic abnormalities, and with adequate tumor and germline DMA specimens for DMA sequence analysis, array-based genomic studies to define copy number changes and uniparental disomy, and arraybased gene expression profiling.
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|Bansal, Dhruv; Vij, Kiran; Chang, Gue Su et al. (2018) Lenalidomide results in a durable complete remission in acute myeloid leukemia accompanied by persistence of somatic mutations and a T-cell infiltrate in the bone marrow. Haematologica 103:e270-e273|
|Xia, Jun; Miller, Christopher A; Baty, Jack et al. (2018) Somatic mutations and clonal hematopoiesis in congenital neutropenia. Blood 131:408-416|
|Wagner, Julia A; Rosario, Maximillian; Romee, Rizwan et al. (2017) CD56bright NK cells exhibit potent antitumor responses following IL-15 priming. J Clin Invest 127:4042-4058|
|Bandyopadhyay, Shovik; Li, Junjie; Traer, Elie et al. (2017) Cholesterol esterification inhibition and imatinib treatment synergistically inhibit growth of BCR-ABL mutation-independent resistant chronic myelogenous leukemia. PLoS One 12:e0179558|
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