Predictors of clinical outcome in myeloproliferative neoplasm, unclassifiable: A Bone Marrow Pathology Group study.

Objectives: Myeloproliferative neoplasm, unclassifiable (MPN-U, revised to MPN, not otherwise specified in the fifth edition of the World Health Organization classification) is a heterogeneous category of primary marrow disorders with clinical, morphologic, and/or molecular features that preclude classification as a more specific MPN subtype due to stage at diagnosis, overlapping features between MPN subtypes, or the presence of coexisting disorders. Compared with other MPN subtypes, the contribution of the mutational landscape in MPN-U in conjunction with other clinical and morphologic biomarkers to prognosis has been less well investigated.

Methods: We performed a multicenter, retrospective study of MPN-U (94 cases) to better define the clinicopathologic features, genetic landscape, and clinical outcomes, including subgroups of early-stage, advanced-stage, and coexisting disorders.

Clinicopathologic Features of IDH2 R172-Mutated Myeloid Neoplasms.

Objectives: IDH1 and IDH2 are among the most commonly mutated genes in myeloid neoplasms (MNs). It has been proposed that IDH2 R172 mutations (mR172) define a molecular subtype of acute myeloid leukemia (AML), but the clinicopathologic features of AML with mR172 have not been fully described.

Methods: We retrospectively identified and characterized all mR172 MNs with increased blasts in our archive for comparison to a similar number of MNs with IDH2 R140 (mR140) and IDH1 R132 (mR132) mutations (n = 39).

The Distinctive Nature of Thyroid MALT Lymphomas Including IRTA1 Expression.

Mucosa-associated lymphoid tissue (MALT) lymphomas often express IgM and IRTA1 with only a minority demonstrating plasmacytic differentiation. However, like primary cutaneous marginal zone lymphoproliferative disorders (PCMZLPD), thyroid MALT lymphomas (T-MALT-L) frequently show plasmacytic differentiation and IgG positivity. Whether T-MALT-L share other features with PCMZLPD, including frequent IgG4 positivity and infrequent IRTA1 expression, and how IRTA1 staining compares to that in Hashimoto thyroiditis (HT) are unknown.

Targeted massively parallel sequencing of mature lymphoid neoplasms: assessment of empirical application and diagnostic utility in routine clinical practice.

Massively parallel sequencing (MPS) has become a viable diagnostic tool to interrogate genetic profiles of numerous tumors but has yet to be routinely adopted in the setting of lymphoma. Here, we report the empirical application of a targeted 40-gene panel developed for use in mature lymphoid neoplasms (MLNs) and report our experience on over 500 cases submitted for MPS during the first year of its clinical use. MPS was applied to both fresh and fixed specimens.

Comparison of therapy-related and de novo core binding factor acute myeloid leukemia: A bone marrow pathology group study.

This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.

ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.

Background We recently found that ARMC 5 variants may be associated with primary aldosteronism in blacks. We investigated a cohort from the MH - GRID (Minority Health Genomics and Translational Research Bio-Repository Database) and tested the association between ARMC 5 variants and blood pressure in black s. Methods and Results Whole exome sequencing data of 1377 black s were analyzed.

Hodgkin lymphoma patients have an increased incidence of idiopathic acquired aplastic anemia.

Idiopathic acquired aplastic anemia (AA) is a rare lymphocyte-mediated bone marrow aplasia. No specific mechanisms or triggers of AA have been identified. We recently observed several patients who developed AA after Hodgkin lymphoma (HL).

Genotype-driven identification of a molecular network predictive of advanced coronary calcium in ClinSeq® and Framingham Heart Study cohorts.

Background: One goal of personalized medicine is leveraging the emerging tools of data science to guide medical decision-making. Achieving this using disparate data sources is most daunting for polygenic traits. To this end, we employed random forests (RFs) and neural networks (NNs) for predictive modeling of coronary artery calcium (CAC), which is an intermediate endo-phenotype of coronary artery disease (CAD).

Same difference: A pilot study of cyclin D1, bcl-2, AMACR, and ALDH-1 identifies significant differences in expression between primary colon adenocarcinoma and its metastases.

Tumor heterogeneity implies the possibility of significantly different expression of key pathways between primary and metastatic clones. Colon adenocarcinoma is one of the few tumors where current practice includes resection of primary and isolated organ metastases simultaneously without neoadjuvant therapy. We performed a pilot study on 28 cases of colon adenocarcinoma resected simultaneously with metastases in patients with no history of neoadjuvant therapy.

Perceived neighborhood problems are associated with shorter telomere length in African American women.

Objectives: African Americans (AA) experience higher levels of stress related to living in racially segregated and poor neighborhoods. However, little is known about the associations between perceived neighborhood environments and cellular aging among adult AA. This study examined whether perceived neighborhood environments were associated with telomere length (TL) in AA after adjustment for individual-level risk factors.

Associations of Apelin, Visfatin, and Urinary 8-Isoprostane With Severe Hypertension in African Americans: The MH-GRID Study.

Background: Apelin is an adipokine directly associated with adiposity, insulin resistance, and decreased blood pressure. Urinary 8-isoprostane is a marker of chronic oxidative endothelial stress. Visfatin, an adipokine that acts by binding and activating the insulin receptor, has been associated with hypertension.

Interpreting conjugated bilirubin levels in newborns.

Objective: To examine the clinical significance of elevated conjugated bilirubin (CB) levels in newborns.

Study Design: This retrospective study evaluated a birth cohort of 271 186 full-term newborns born within a Northern California hospital network from 1995 to 2004. All CB and direct bilirubin (DB) levels were available in a database and were correlated with the patients' inpatient and outpatient International Classification of Diseases, 9th Revision diagnoses.

Expression differences by continent of origin point to the immortalization process.

Analysis of recently available microarray expression data sets obtained from immortalized cell lines of the individuals represented in the HapMap project have led to inconclusive comparisons across cohorts with different ancestral continent of origin (ACOO). To address this apparent inconsistency, we applied a novel approach to accentuate population-specific gene expression signatures for the CEU [homogeneous US residents with northern and western European ancestry (HapMap samples)] and YRI [homogenous Yoruba people of Ibadan, Nigeria (HapMap samples)] trios. In this report, we describe how four independent data sets point to the differential expression across ACOO of gene networks implicated in transforming the normal lymphoblast into immortalized lymphoblastoid cells.

Nontransplant surgical interventions in progressive familial intrahepatic cholestasis.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a family of rare childhood diseases that was universally fatal until the development of liver transplant. In the last 20 years, the use of nontransplant surgery to treat PFIC has become the standard of care. There are various surgical techniques that have been performed.

Data structures and algorithms for analysis of genetics of gene expression with Bioconductor: GGtools 3.x.

Summary: Associations between DNA polymorphisms and mRNA abundance are a natural target of genetic investigations, and microarrays facilitate genome-wide and transcriptome-wide surveys of these associations. This work is motivated by emerging requirements for data architectures and algorithm interfaces to allow flexible exploration of public and private archives of genotyping and expression arrays. Using R/Bioconductor facilities, Phase II HapMap genotypes and Illumina 47K expression assay results archived on multiple populations may be interactively explored and analyzed using commodity hardware.