International external quality assurance of JAK2 V617F quantification.

External quality assurance (EQA) programs are vital to ensure high quality and standardized results in molecular diagnostics. It is important that EQA for quantitative analysis takes into account the variation in methodology. Results cannot be expected to be more accurate than limits of the technology used, and it is essential to recognize factors causing substantial outlier results.

Impact of Graft-Versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation.

Background: Natural killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often HLA class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by killer cell immunoglobulin-like receptor (KIR)-HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT.

Acute cytotoxicity of MIRA-1/NSC19630, a mutant p53-reactivating small molecule, against human normal and cancer cells via a caspase-9-dependent apoptosis.

Although numerous studies have focused on the mechanisms of action of the candidate chemotherapeutic drug MIRA-1/NSC19630, initially described as a mutant p53-reactivating small molecule, the issue of its toxicological evaluation remains open. Here, we devised a strategy to examine the effects of MIRA-1 on a variety of human normal cells and cancer cell lines. First, we demonstrated a massive and rapid (within 2 hours) MIRA-1 apoptotic effect on human normal primary epithelial cells as shown using an intestinal mucosa explant assay.

Complete donor T cell chimerism predicts lower relapse incidence after standard double umbilical cord blood reduced-intensity conditioning regimen allogeneic transplantation in adults.

Double umbilical cord blood (dUCB) allogeneic transplantation after a low-dose total body irradiation, cyclophosphamide, and fludarabine (TCF)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there are little data regarding the long-term outcome of CD3(+) T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases who received dUCB allogeneic transplants conditioned with TCF were included in this retrospective study.

Human herpesvirus 6 reactivation before engraftment is strongly predictive of graft failure after double umbilical cord blood allogeneic stem cell transplantation in adults.

Our main objective was to determine new factors associated with engraftment and single-unit predominance after double umbilical cord blood (UCB) allogeneic stem-cell transplantation. Engraftment occurred in 78% of cases in this retrospective study including 77 adult patients. Three-year overall survival, disease-free survival, relapse incidence, and nonrelapse mortality were 55 ± 6%, 44 ± 6%, 33 ± 5%, and 23 ± 4%, respectively.

PRIMA-1Met induces myeloma cell death independent of p53 by impairing the GSH/ROS balance.

The aim of this study was to assess the efficiency of p53 reactivation and induction of massive apoptosis (PRIMA-1(Met)) in inducing myeloma cell death, using 27 human myeloma cell lines (HMCLs) and 23 primary samples. Measuring the lethal dose (LD50) of HMCLs revealed that HMCLs displayed heterogeneous sensitivity, with an LD50 ranging from 4 μM to more than 200 μM. The sensitivity of HMCLs did not correlate with myeloma genomic heterogeneity or TP53 status, and PRIMA-1(Met) did not induce or increase expression of the p53 target genes CDKN1A or TNFRSF10B/DR5.

NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML.

Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34(+) bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins.

New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance.

Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent the second malignant primary bone tumor of adults after osteosarcoma, but in contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. Few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown.

The translocation t(4;14) can be present only in minor subclones in multiple myeloma.

Purpose: Although the translocation t(4;14) is supposed to be a primary event in multiple myeloma, we have been surprised to observe that in large relapse series of patients, the t(4;14) can be observed only in subpopulations of plasma cells, in contrast to what is seen at diagnosis. This observation raised the question of possible subclones harboring the translocation that would be observable only at the time of relapse.

Experimental Design: To address this issue, we analyzed by FISH a cohort of 306 patients for whom we had at least two samples obtained at different disease phases.

Comparison of outcomes after two standards-of-care reduced-intensity conditioning regimens and two different graft sources for allogeneic stem cell transplantation in adults with hematologic diseases: a single-center analysis.

Recent advances in allogeneic stem cell transplantation (allo-HSCT) have included the advent of reduced-intensity conditioning (RIC) regimens to decrease the toxicity of myeloablative allo-SCT and the use of double umbilical cord blood (dUCB) units as a graft source in adults lacking a suitable donor. The FB2A2 regimen (fludarabine 30 mg/kg/day for 5-6 days + i.v.

Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma.

Deletion of the 17p13 chromosomal region [del(17p)] is associated with a poor outcome in multiple myeloma. Most of the studies have targeted the TP53 gene for deletion analyses, although no study showed that this gene is the deletion target. In order to address this issue, we sequenced the TP53 gene in 92 patients with multiple myeloma at diagnosis, 54 with a del(17p) and 38 lacking del(17p).

Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome.

Purpose: Survival of patients with multiple myeloma is highly heterogeneous, from periods of a few weeks to more than 10 years. We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers.

Patients And Methods: In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival.

Surface-enhanced laser desorption/ionization time of flight mass spectrometry protein profiling identifies ubiquitin and ferritin light chain as prognostic biomarkers in node-negative breast cancer tumors.

Novel prognostic biomarkers are imperatively needed to help direct treatment decisions by typing subgroups of node-negative breast cancer patients. The current study has used a proteomic approach of SELDI-TOF-MS screening to identify differentially cytosolic expressed proteins with a prognostic impact in 30 node-negative breast cancer patients with no relapse versus 30 patients with metastatic relapse. The data analysis took into account 73 peaks, among which 2 proved, by means of univariate Cox regression, to have a good cumulative prognostic-informative power.