Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia.

Chemotherapy resistance is the main cause of treatment failure in acute myeloid leukemia (AML) and has been related to ATP-binding cassette (ABC) transporter activity. However, the links between ABC activity, immunophenotype, and molecular AML parameters have been poorly evaluated. Moreover, the prognostic value of ABC activity, when compared to new molecular markers, is unknown.

Dyadic Coping in Couples Facing Chronic Physical Illness: A Systematic Review.

Chronic physical illness affects not only patients but also their partners. Dyadic coping (DC)-the ways couples cope in dealing with a stressor such as chronic illness-has received increased attention over the last three decades. The aim of the current study was to summarize the state of research on DC in couples with chronic physical illnesses.

CD28/4-1BB CD123 CAR T cells in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is associated with a remarkably poor prognosis and with no treatment consensus. The identification of relevant therapeutic targets is challenging. Here, we investigated the immune functions, antileukemia efficacy and safety of CD28/4-1BB CAR T cells targeting CD123 the interleukin (IL)-3 receptor alpha chain which is overexpressed on BPDCN.

How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed.

T-cell prolymphocytic leukemia and tuberculosis: a puzzling association.

T-cell prolymphocytic leukemia can result in severe immune T-cell deficiency. Clinicians should be aware of this complication in this rare lymphoid malignancy, and opportunistic infections should be ruled out before the use of usual immunosuppressive procedures such as alemtuzumab and hematopoietic stem cell transplantation.

Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study.

The spectrum of chronic CD8+ T-cell expansions: clinical features in 14 patients.

Chronic CD8(+) T-cell expansions can result in parotid gland swelling and other organ infiltration in HIV-infected patients, or in persistent cytopenias. We report 14 patients with a CD8+ T-cell expansion to better characterize the clinical spectrum of this ill-defined entity. Patients (9 women/5 men) were 65 year-old (range, 25-74).

[Polyclonal CD8+/CD57+ T cell expansions: clinical significance].

Polyclonal CD8(+)/CD57(+)T cell lymphocytosis can be observed in various conditions such as chronic viral infections, autoimmune cytopenias, connective tissue diseases, chronic graft-versus-host disease and primary or secondary immune deficiencies. This population results from the chronic stimulation of CD8(+)/CD28(+)/CD57(-)lymphocytes by exogenous (mostly infection-related), autologous or allogeneic antigens. Paralleling chronic antigen stimulation, these CD8(+) T cells acquire a poor capacity to proliferate in standard conditions in relation with the loss of CD28, whereas CD57 antigen becomes expressed at their surface.

Mast cell leukemia: identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine kinase inhibitor.

Objective: Most patients with systemic mastocytosis bear mutations in the tyrosine kinase receptor gene c-Kit. Limited treatment options exist for mast cell leukemia, a rare form of systemic mastocytosis associated with a dire prognosis. Our aim was to investigate c-Kit mutations associated with mast cell leukemia and find new treatment for this severe form of mastocytosis.

Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance.

Background: The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome.

Design And Methods: Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry.

Blood CD34-c-Kit+ cell rate correlates with aggressive forms of systemic mastocytosis and behaves like a mast cell precursor.

Mastocytosis is a heterogeneous disease characterized by the accumulation of mast cells in one or more organs. Our objective was to identify a peripheral mast cell precursor and assess its variation rate in mastocytosis. A peripheral blood phenotypic analysis was performed among 50 patients with mastocytosis who were enrolled in a prospective multicentric French study, and the phenotypic analysis results of the patients were compared with those of healthy donors.

Systemic mastocytosis and bone involvement in a cohort of 75 patients.

Objectives: To investigate bone involvement in a large cohort of systemic mastocytosis (SM) patients, and evaluate the efficacy of bisphosphonate therapy.

Patients And Methods: From 2000 to 2004, 75 patients with SM according to WHO criteria underwent skeletal x-rays and bone mineral density (BMD) assessment. Sequential BMD assessments were performed in nine patients treated with bisphosphonate (mean follow-up 65 months).

Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.

Adult mastocytosis is an incurable clonal disease associated with c-KIT mutations, mostly in exon 17 (D816V). In contrast, pediatric mastocytosis often spontaneously regresses and is considered a reactive disease. Previous studies on childhood mastocytosis assessed only a few patients and focused primarily on codon 816 mutations, with various results.

Acute left ventricular dilatation and shock-induced myocardial dysfunction.

Objective: Whether cardiac ventricles can acutely dilate during septic myocardial dysfunction.

Design: A prospective echocardiographic study was performed to assess changes of left ventricular dimensions over time in patients with septic shock.

Settings: A 20-bed surgical intensive care unit of Pitié-Salpêtrière university hospital in Paris.

Isolated and reversible impairment of ventricular relaxation in patients with septic shock.

Objective: Many patients with septic shock and increased cardiac troponin I (cTnI) do not exhibit significant left ventricular systolic dysfunction. We hypothesized that an isolated and reversible impairment of ventricular relaxation may be associated with the increase in cTnI.

Design: Prospective, observational study.

[Applications of molecular biology to care of patients with malignant hematological disease].

The improvement of the techniques of molecular biology allowed greater performances in the field of detection and characterization of chromosomal abnormalities and/or molecular defects observed in human hematological malignancies. Cytological and immunophenotypical results are reinforced by data obtained with standard and molecular cytogenetic tools and with PCR based techniques. Molecular data are usefull at diagnosis in order to define different types of leukemias and to score patient prognosis.

Solid-phase synthesis and evaluation of libraries of substituted 4,5-dihydropyridazinones as vasodilator agents.

The solid-phase parallel preparation of a library of 4,5-dihydropyridazin-3(2H)-one derivatives substituted at position 6 with piperazinylmethyl or tetrahydroquinolinylmethyl groups and analogues (3) is reported. Polymer-supported gamma-keto-delta-aminoesters prepared from Wang resin reacted with hydrazine or methylhydrazine to afford pyridazinones in good yields after a cyclization cleavage approach. We have evaluated these novel analogues and several compounds of other series (1, 2) for their vasorelaxant effect.

Effect of tyrosine kinase inhibitor STI571 on the kinase activity of wild-type and various mutated c-kit receptors found in mast cell neoplasms.

Systemic mastocytosis (SM) is a rare disease caused by an abnormal mast cell accumulation in various tissues. Two classes of constitutive activating c-kit mutations are found in SM. The most frequent class occurs in the catalytic pocket coding region with substitutions at codon 816 and the other in the intracellular juxtamembrane coding region.

Kit and c-kit mutations in mastocytosis: a short overview with special reference to novel molecular and diagnostic concepts.

Mastocytosis is a heterogeneous group of hematopoietic disorders characterized by abnormal growth and accumulation of mast cells (MC) in one or more organs. Clinical symptoms occur as a result of the release of chemical mediators and/or of pathologic infiltration of MC in various tissues. Although the initial events leading to mastocytosis have not yet been unraveled, acquired alterations in the c-kit gene coding for the receptor of stem cell factor (SCF), a major cytokine involved in MC growth, have been described in a significant number of patients.

The role of mast cells in host defense and their subversion by bacterial pathogens.

Mast cells (MCs) play a prominent role in the early immune response to invading pathogenic bacteria. This newly discovered role for MCs involves the release of chemoattractants that recruit neutrophils and the direct phagocytosis and killing of opsonized bacteria. Whereas these activities are clearly beneficial to the host, certain pathogens have evolved mechanisms to evoke anomalous MC responses to the detriment of the host.