Biopsy of nodular skin lesion at the diagnosis () and after treatment ()

<p><b>Copyright information:</b></p><p>Taken from "Update on the treatment of disseminated fusariosis: Focus on voriconazole"</p><p></p><p>Therapeutics and Clinical Risk Management 2007;3(6):1165-1173.</p><p>Published online Jan 2007</p><p>PMCID:PMC2387295.</p><p>© 2007 Dove Medical Press Limited. All rights reserved</p

Additional file 1: Table S1. of Physicians’ attitude towards selection of second line therapy with nilotinib and dasatinib in chronic myeloid leukemia patients

Physician characteristics. (DOCX 15 kb

Impact of posaconazole prophylaxis on the incidence and mortality of invasive mold disease in the 2009-2012 validation cohort.

<p>(a) Cumulative incidence of invasive mold disease in patients with calculated risk scores <6 or > 6. <i>P</i> value determined by Chi-square test. (b) Kaplan-Meier analysis of crude mortality in patients with acute myelogenous leukemia or myelodysplastic syndrome undergoing remission-induction chemotherapy by status of posaconazole prophylaxis. Each patient is analyzed only once and was classified as alive or dead at the time of discharge (censored) or death by day +42 after admission. <i>P</i> value was determined by the Mantel-Cox (log-rank) test.</p

Distribution of risk scores versus the cumulative incidence of proven or probable invasive mold disease.

<p>Distribution of risk scores versus the cumulative incidence of proven or probable invasive mold disease.</p

Analysis of risk score discrimination and optimal cut-off for invasive model disease risk.

<p>(a) Receiver-operator curve (ROC) analysis plot of the true positives plotted as a function of the false-positives (100-specificity) at different cutoffs of the risk score. Gray bands represent the 95% CI of the plot. The dotted line represents a reference line no discrimination for invasive mold disease (aROC=0.5). The <i>P</i> value is the probability that the aROC differs significantly from aROC=0.5; (b) Plot of sensitivity and specificity versus risk score. The highest sensitivity (true positive rate) and specificity (true negative rate) meet at a score just below 6, suggesting a criterion value of > 6.</p

IKAROS Deletions Dictate a Unique Gene Expression Signature in Patients with Adult B-Cell Acute Lymphoblastic Leukemia

<div><h3>Background</h3><p>Deletions of IKAROS (<em>IKZF1</em>) frequently occur in B-cell precursor acute lymphoblastic leukemia (B-ALL) but the mechanisms by which they influence pathogenesis are unclear. To address this issue, a cohort of 144 adult B-ALL patients (106 <em>BCR-ABL1</em>-positive and 38 B-ALL negative for known molecular rearrangements) was screened for <em>IKZF1</em> deletions by single nucleotide polymorphism (SNP) arrays; a sub-cohort of these patients (44%) was then analyzed for gene expression profiling.</p> <h3>Principal Findings</h3><p>Total or partial deletions of <em>IKZF1</em> were more frequent in <em>BCR-ABL1</em>-positive than in <em>BCR-ABL1</em>-negative B-ALL cases (75% <em>vs</em> 58%, respectively, p = 0.04). Comparison of the gene expression signatures of patients carrying <em>IKZF1</em> deletion <em>vs</em> those without showed a unique signature featured by down-regulation of B-cell lineage and DNA repair genes and up-regulation of genes involved in cell cycle, <em>JAK-STAT</em> signalling and stem cell self-renewal. Through chromatin immunoprecipitation and luciferase reporter assays we corroborated these findings both <em>in vivo</em> and <em>in vitro</em>, showing that Ikaros deleted isoforms lacked the ability to directly regulate a large group of the genes in the signature, such as <em>IGLL1</em>, <em>BLK</em>, <em>EBF1</em>, <em>MSH2, BUB3, ETV6, YES1, CDKN1A</em> (p21), <em>CDKN2C</em> (p18) and <em>MCL1</em>.</p> <h3>Conclusions</h3><p>Here we identified and validated for the first time molecular pathways specifically controlled by <em>IKZF1</em>, shedding light into <em>IKZF1</em> role in B-ALL pathogenesis.</p> </div

The Ik6 isoform cannot regulate transcription of the <i>EBF1, MSH2, and MCL1</i> promoters in a transient luciferase assay.

<p>A) Western blotting of Ik1 and Ik6 proteins transiently expressed by respective vectors when transfected into HEK-293 cells. B) Left: schematic representation of the promoters cloned upstream of the pGL3basic-Luciferase vector. Right: relative luciferase activity of the reporters determined by co-transfection with either an Ik6 or an Ik1 expression vector as compared to that obtained with the empty vector which was arbitrarily set to 1. Results represent the average of three independent experiments.</p

JAK-STAT5 signalling in Ikaros-rearranged ALL.

<p>Western Blot analysis of STAT5 in <i>IKZF1</i> deleted and wild-type leukemia primary cells (A) showed an increased phosphorylation of STAT5 in cells with Ikaros deletion. This was correlated with an increased production of Bcl-xl (B) as determined by RQ-PCR. (C) Western Blot analysis showed a marked increased phosphorylation of histone H2A.X in leukemia cells with Ikaros deletion compared to normal <i>IKZF1</i> cells. Abbreviations: LC indicates leukemia cells. β-ACTIN was used as a loading control of the WB.</p

<i>IKZF1</i> deletion patterns in adult ALL patients.

<p>Schematic representation of the <i>IKZF1</i> gene on chromosome 7p12, with coding exons (ex) in gray and the first non-coding exon in white. N-terminal zinc-fingers (F1–F4) show DNA-binding activity and C-terminal ones (F5–F6) mediate dimerization of the protein. Black segment reports indicate the genomic extent of the <i>IKZF1</i> deletions of the most common deletions. Percentage is reported for each type of deletion.</p

Demographics and Clinical Characteristics of patients with B-progenitor positive Acute Lymphoblastic Leukemia.

<p>Demographics and Clinical Characteristics of patients with B-progenitor positive Acute Lymphoblastic Leukemia.</p