La cytotoxicité à médiation cellulaire de type Natural killer et la voie membranolytique de la perforine

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

ABCG2, Cytogenetics, and Age Predict Relapse after Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission

Recent studies have shown that ABGG2 protein overexpression in acute myeloid leukemia (AML) may be associated with poor response to therapy and increased relapse risk. Few data are available in patients with AML undergoing allogeneic stem cell transplantation (SCT), particularly when in complete remission (CR). We analyzed 105 patients with AML who underwent allogeneic SCT in CR evaluating the role of ABCG2 and other pretransplantation features on subsequent transplantation outcomes. Factors negatively associated with leukemia-free survival (LFS) were unfavorable cytogenetics (3-year LFS 48% versus 80%, P =.0035) and ABCG2 positivity (65% versus 80%, P =.045). Three-year cumulative incidence of relapse (CIR) in the whole population was 20%; a higher incidence of relapse was associated with adverse cytogenetics (41% versus 16%, P =.018), ABCG2 overexpression (29% versus 15%, P =.04), and, marginally, age > 50 years (30% versus 14%, P =.06). We grouped patients according to the combination of these 3 risk factors: no patient relapsed within 3 years from SCT in the group without risk factors, whereas the 3-year CIR was 12% (95% confidence interval [CI], 2% to 25%) in the group with 1 risk factor and 47% (95% CI, 31% to 70%) in patients with 2 or 3 risk factors (P =.00005). In conclusion, allogeneic SCT does not seem to abrogate the negative prognosis associated with ABCG2 overexpression at diagnosis, specifically in terms of a higher relapse risk. ABCG2, age, and cytogenetics can predict AML relapse after SCT in patients who undergo transplantation while in CR. \ua9 2016 American Society for Blood and Marrow Transplantatio

The prognostic value of P-glycoprotein (ABCB) and breast cancer resistance protein (ABCG2) in adults with de novo acute myeloid leukemia with normal karyotype

Multidrug resistance is a major cause of treatment failure in acute myeloid leukemia (AML). P-glycoprotein (PGP) over-expression has an unfavorable prognostic significance, while the role of breast cancer resistance protein (BCRP) is less clear, especially in AML patients with a normal karyotype. We studied 73 consecutive AML patients with a normal karyotype. BCRP was over-expressed in 24 patients (33%) and was significantly co-expressed with PGP (13/24 vs 11/49, p=0.006) and with CD56. Only PGP, along with age and CD34, affected the achievement of complete remission (p=0.02), while BCRP-positive cases showed an increased risk of relapse (p=0.005) and a shorter disease-free survival (p=0.027). BCRP over-expression did not influence the achievement of remission, but significantly affected the duration of complete remissions. BCRP may, therefore, be regarded as a prognostic factor in patients with normal karyotype AML, for the design of risk-adapted post-remission therapy

Comparison of the latest commercial short and long oligonucleotide microarray technologies

Abstract Background We compared the relative precision and accuracy of expression measurements obtained from three different state-of-the-art commercial short and long-oligonucleotide microarray platforms (Affymetrix GeneChip™, GE Healthcare CodeLink™ and Agilent Technologies). The design of the comparison was chosen to judge each platform in the context of a multi-project program. Results All wet-lab experiments and raw data acquisitions were performed independently by each commercial platform. Intra-platform reproducibility was assessed using measurements from all available targets. Inter-platform comparisons of relative signal intensities were based on a common and non-redundant set of roughly 3,400 targets chosen for their unique correspondence toward a single transcript. Despite many examples of strong similarities we found several areas of discrepancy between the different platforms. Conclusion We found a higher level of reproducibility from one-color based microarrays (Affymetrix and CodeLink) compared to the two-color arrays from Agilent. Overall, Affymetrix data had a slightly higher level of concordance with sample-matched real-time quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) data particularly for detecting small changes in gene expression levels.</p

High CD200 expression is associated with poor prognosis in cytogenetically normal acute myeloid leukemia, even in FlT3-ITD-/NPM1+ patients

Overexpression of CD200, a trans-membrane protein belonging to the immunoglobulin superfamily, has been associated with poor prognosis in patients with acute myeloid leukemia (AML). As few data are available in the subset of cytogenetically-normal (CN) AML, we retrospectively evaluated the correlations between CD200 expression and response to therapy in a series of 139 adults with CN-AML. CD200 was expressed in 67/139 (48%) cases; 18 of them (28%) expressed CD200 at high intensity. No differences in CD200 expression rate were observed according to age, WBC count, type of leukemia, FLT3 or NMP1 mutation, and CD56 expression. A higher incidence of CD200 expression was observed in CD34+ cases (P < 0.0001) and in BCL2+ patients (P = 0.04). Complete remission (CR) was evaluable achieved in 98 patients (70%): 56/71 (79%) in CD200- and 47/67 (63%) in CD200+ patients (P = 0.03), with a lower CR rate in patients with high CD200 intensity (9/18, 50%). CD200 expression had a negative impact on long-term outcome. CD200 expression, per se, did not impact on disease-free survival (DFS), but cases with high CD200 expression had a lower 3-year DFS compared to CD200-negative and low-expressing ones (0% vs 65% vs 68%, P = 0.019). Three-year overall survival (OS) was 51% in CD200- and 27% in CD200+ patients (P = 0.01), with a significant difference among cases with low or high CD200 expression (35% vs 0%, P = 0.001). CD200 high expression defined a group with very poor DFS and OS also among the 37 FLT3-/NPM1+: 3-year DFS and OS were 88% and 60% in CD200-, 50% and 32% in CD200 low and 0% and 0% in CD200 high patients, respectively (P = 0.01 for DFS and P = 0.05 for OS). Our data suggest a negative impact of CD200 expression in CN-AML, with a further worsening in high-expressing cases, also in the subset of FLT3-/NPM1+ patients

High CD200 expression is associated with poor prognosis in cytogenetically normal acute myeloid leukemia, even in FlT3-ITD-/NPM1+ patients

Overexpression of CD200, a trans-membrane protein belonging to the immunoglobulin superfamily, has been associated with poor prognosis in patients with acute myeloid leukemia (AML). As few data are available in the subset of cytogenetically-normal (CN) AML, we retrospectively evaluated the correlations between CD200 expression and response to therapy in a series of 139 adults with CN-AML. CD200 was expressed in 67/139 (48%) cases; 18 of them (28%) expressed CD200 at high intensity. No differences in CD200 expression rate were observed according to age, WBC count, type of leukemia, FLT3 or NMP1 mutation, and CD56 expression. A higher incidence of CD200 expression was observed in CD34+ cases (P < 0.0001) and in BCL2+ patients (P = 0.04). Complete remission (CR) was evaluable achieved in 98 patients (70%): 56/71 (79%) in CD200- and 47/67 (63%) in CD200+ patients (P = 0.03), with a lower CR rate in patients with high CD200 intensity (9/18, 50%). CD200 expression had a negative impact on long-term outcome. CD200 expression, per se, did not impact on disease-free survival (DFS), but cases with high CD200 expression had a lower 3-year DFS compared to CD200-negative and low-expressing ones (0% vs 65% vs 68%, P = 0.019). Three-year overall survival (OS) was 51% in CD200- and 27% in CD200+ patients (P = 0.01), with a significant difference among cases with low or high CD200 expression (35% vs 0%, P = 0.001). CD200 high expression defined a group with very poor DFS and OS also among the 37 FLT3-/NPM1+: 3-year DFS and OS were 88% and 60% in CD200-, 50% and 32% in CD200 low and 0% and 0% in CD200 high patients, respectively (P = 0.01 for DFS and P = 0.05 for OS). Our data suggest a negative impact of CD200 expression in CN-AML, with a further worsening in high-expressing cases, also in the subset of FLT3-/NPM1+ patient

Determining the Set of Items to Include in Breast Operative Reports, Using Clustering Algorithms on Retrospective Data Extracted from Clinical DataWarehouse

International audienceMedical reports are key elements to guarantee the quality, and continuity of care but their quality remains an issue. Standardization and structuration of reports can increase their quality, but are usually based on expert opinions. Here, we hypothesize that a structured model of medical reports could be learnt using machine learning on retrospective medical reports extracted from clinical data warehouses (CDW). To investigate our hypothesis, we extracted breast cancer operative reports from our CDW. Each document was preprocessed and split into sentences. Clustering was performed using TFIDF, Paraphrase or Universal Sentence Encoder along with K-Means, DBSCAN, or Hierarchical clustering. The best couple was TFIDF/K-Means, providing a sentence coverage of 89 % on our dataset; and allowing to identify 7 main categories of items to include in breast cancer operative reports. These results are encouraging for a document preset creation task and should then be validated and implemented in real life