Understanding the dynamics and spread of human immunodeficiency virus type 1 (HIV-1) within the body, including within the female genital tract with its central role in heterosexual and peripartum transmission, has important implications for treatment and vaccine development. To study HIV-1 populations within tissues, we compared viruses from across the cervix to those in peripheral blood mononuclear cells (PBMC) during effective and failing antiretroviral therapy (ART) and in patients not receiving ART. Single-genome sequences of the C2-V5 region of HIV-1 env were derived from PBMC and three cervical biopsies per subject. Maximumlikelihood phylogenies were evaluated for differences in genetic diversity and compartmentalization within and between cervical biopsies and PBMC. All subjects had one or more clades with genetically identical HIV-1 env sequences derived from single-genome sequencing. These sequences were from noncontiguous cervical biopsies or from the cervix and circulating PBMC in seven of eight subjects. Compartmentalization of virus between genital tract and blood was observed by statistical methods and tree topologies in six of eight subjects, and potential genital lineages were observed in two of eight subjects. The detection of monotypic sequences across the cervix and blood, especially during effective ART, suggests that cells with provirus undergo clonal expansion. Compartmentalization of viruses within the cervix appears in part due to viruses homing to and/or expanding within the cervix and is rarely due to unique viruses evolving within the genital tract. Further studies are warranted to investigate mechanisms producing monotypic viruses across tissues and, importantly, to determine whether the proliferation of cells with provirus sustain HIV-1 persistence in spite of effective ART.Immune and drug pressures modify the human immunodeficiency virus type 1 (HIV-1) population within an individual and, along with physical barriers in the body, may result in uneven selective pressures between tissues, allowing the evolution of tissue-specific viral variants. Whether unique viruses evolve within the genital tract, the tissue involved in most cases of HIV-1 transmission, is relevant to developing vaccines and other interventions to reduce HIV-1 transmission. Compartmentalization is the term applied to genetically distinct HIV-1 populations in different tissues. Compartmentalization of genital tract compared to blood HIV-1 has been observed in 50 to 75% of men and women (6,9,12,13,19,21,22,29,31,33,34,41,42,48).In a study of compartmentalization in the female genital tract, we noted that HIV-1 DNA sequences from the female genital tract clustered in phylograms, suggestive of a burst of replication with spread to adjacent cells in the cervix (M. E. Bull, G. H. Learn, I. Genowati, J. L. McKernan, J. Hitti, D. Lockhart, S. Holte, J. Dragavon, R. W. Coombs, J. I. Mullins, and L. M. Frenkel, submitted for publication). We suspected that the low viral diversity was due to the small size of the biopsies, t...

BACKGROUND Chromosomal abnormalities are important in the diagnosis and prognosis of patients with acute myeloid leukemia (AML). Genomic microarray techniques detect recurrent copy‐neutral loss of heterozygosity (cnLOH) in addition to copy number aberrations. However, the clinical utility has not been fully established. Therefore, in the current study, the authors examined the prognostic impact of acquired cnLOH in patients with AML, including complete remission (CR) rate, duration of CR, and overall survival (OS). METHODS A total of 112 consecutive patients with AML who were undergoing chromosome genomic array testing (CGAT) at the Seattle Cancer Care Alliance were included in the current study. DNA from the bone marrow or blood was analyzed with a microarray platform with both single‐nucleotide polymorphism (SNP) probes and non‐SNP probes to identify acquired cnLOH. Results were correlated with cytogenetic, molecular, immunophenotypic, and other clinicopathological findings. RESULTS Patients with cnLOH demonstrated a shorter duration of CR (hazard ratio, 1.87; P =.04) and worse OS (HR, 1.82; P = .03). Multivariate analyses confirmed the independent predictive value of cnLOH for early disease recurrence (P =.02). These results largely reflected those in patients with intermediate and unfavorable cytogenetics. Most strikingly, 13q cnLOH was found to demonstrate a 6.64‐fold higher rate of disease recurrence (P =.006) and 3.45‐fold worse OS (P = .02) and was enriched with the FLT3‐ITD (Fms‐related tyrosine kinase 3‐internal tandem duplication) mutation. CONCLUSIONS CnLOH has important prognostic significance in patients with AML. CGAT can replace imbalance fluorescence in situ hybridization and the authors recommend the routine use of CGAT to detect cnLOH, particularly among patients with intermediate‐risk cytogenetics. Cancer 2015;121:2900–2908. © 2015 American Cancer Society.

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