Differences in Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia.

Background: Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates.

Materials And Methods: Using an test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone.

Ruxolitinib in combination with prednisone and nilotinib exhibit synergistic effects in human cells lines and primary cells from myeloproliferative neoplasms.

Ruxolitinib is the front-line non-palliative treatment for myelofibrosis (MF). However, a significant number of patients lose or present suboptimal response, are resistant or have unacceptable toxicity. In an attempt to improve response and avoid the adverse effects of this drug, we evaluated the combination of 17 drugs with ruxolitinib in models of peripheral blood mononuclear cells from MF patients and cell lines.

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients.

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study.

Dasatinib as a bone-modifying agent: anabolic and anti-resorptive effects.

Background: Bone loss, in malignant or non-malignant diseases, is caused by increased osteoclast resorption and/or reduced osteoblast bone formation, and is commonly associated with skeletal complications. Thus, there is a need to identify new agents capable of influencing bone remodeling. We aimed to further pre-clinically evaluate the effects of dasatinib (BMS-354825), a multitargeted tyrosine kinase inhibitor, on osteoblast and osteoclast differentiation and function.

Isolation and characterization of mesenchymal stromal cells from human degenerated nucleus pulposus: comparison with bone marrow mesenchymal stromal cells from the same subjects.

Study Design: To identify mesenchymal stromal cells (MSC) from degenerate human nucleus pulposus (NP) and compare them with bone marrow (BM) MSC.

Objective: To test whether MSC obtained from NP and BM from the same subjects share similar biologic characteristics.

Summary Of Background Data: Recent studies have proposed biologic strategies for the treatment of intervertebral disc degeneration, including cell therapy.

Immunomodulatory effect of 5-azacytidine (5-azaC): potential role in the transplantation setting.

Cytokine genes are targets of multiple epigenetic mechanisms in T lymphocytes. 5-azacytidine (5-azaC) is a nucleoside-based DNA methyltransferase inhibitor that induces demethylation and gene reactivation. In the current study, we analyzed the effect of 5-azaC in T-cell function and observed that 5-azaC inhibits T-cell proliferation and activation, blocking cell cycle in the G(0) to G(1) phase and decreasing the production of proinflammatory cytokines such as tumor necrosis factor-alpha and interferon-gamma.

Both CD133(+) cells and monocytes provide significant improvement for hindlimb ischemia, although they do not transdifferentiate into endothelial cells.

To address a number of questions regarding the experimental use of bone marrow (BM) stem cells in hindlimb ischemia, including which is the best cell type (e.g., purified hematopoietic stem cell or monocytes), the best route of delivery [intramuscular (IM) or intravenous (IV)], and the mechanism of action (transdifferentiation or paracrine effects), we have compared the neovascularization capacities of CD133(+) stem cells and monocytes (CD11b(+)) from the BM of Tie2-GFP mice either via IV or IM in a murine severe hindlimb ischemia model.

Treatment with bortezomib of human CD4+ T cells preserves natural regulatory T cells and allows the emergence of a distinct suppressor T-cell population.

Background: In vitro depletion of alloreactive T cells using the proteasome inhibitor bortezomib is a promising approach to prevent graft-versus-host disease after allogeneic stem cell transplantation. We have previously described the ability of bortezomib to selectively eliminate alloreactive T cells in a mixed leukocyte culture, preserving non-activated T cells. Due to the role of regulatory T cells in the control of graft versus host disease, in the current manuscript we have analyzed the effect of bortezomib in regulatory T cells.

Immunophenotypical, morphologic, and functional characterization of maturation-associated plasmacytoid dendritic cell subsets in normal adult human bone marrow.

Background: Information about maturation of plasmacytoid dendritic cell precursors (pre-pDCs) in normal bone marrow (BM) remains limited.

Study Design And Methods: Immunophenotypical, morphologic, and functional changes associated with maturation of pre-pDCs were analyzed in adult normal human BM (n = 45).

Results: Three pre-pDC maturation stages, with an increasingly higher degree of maturity, were systematically identified: CD34++/HLA-DR++/+++/CD123++/CD45+/++ (Stage I), CD34+/HLA-DR+/++/CD123++/+++/CD45+/++ (Stage II), and CD34-/HLA-DR++/CD123++/+++/CD45++ (Stage III) cells.

[Paroxysmal nocturnal hemoglobinuria].

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder characterized by the existence of somatic mutations in the PIG-A (phosphatidylinositolglycan complementation class A) gene, which encodes for a protein involved in the biosynthesis of the glycosyl phosphatidylinositol (GPI) molecule that serves as an anchor for many cell surface proteins. This genetic alteration translates into a total or partial deficiency in the PNH clone of surface proteins attached to the cell by a GPI anchor. Evaluation of deficient expression of GPI-associated proteins is currently used for the diagnosis of paroxysmal nocturnal hemoglobinuria.

Detailed immunophenotypic characterization of different major and minor subsets of peripheral blood cells in patients with paroxysmal nocturnal hemoglobinuria.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a deficient expression of glycosylphosphatidylinositol-anchored proteins (GPI-APs), due to somatic mutations of the phosphatidylinositolglycan complementation Class A (PIG-A) gene.

Study Design And Methods: In this study, the expression of a high number of GPI-APs on different subsets of peripheral blood (PB) cells from 14 PNH patients and their potential association with underlying genetic abnormalities has been analyzed.

Results: This study confirms the existence of variable patterns of expression of different GPI-APs on both major and minor PB-cell subsets from PNH patients.

Quantitative analysis of the expression of glycosylphosphatidylinositol-anchored proteins during the maturation of different hematopoietic cell compartments of normal bone marrow.

Background: Glycosylphosphatidylinositol-anchored proteins (GPI-AP) are a heterogeneous group of proteins deficiently expressed in patients with paroxysmal nocturnal hemoglobinuria. Up till now, no study has been reported in which the exact patterns of expression of a large number of GPI-AP are quantitatively evaluated in normal bone marrow (BM) cells classified according to their lineage and maturation stage.

Methods: In the present study, we have quantitatively analyzed the expression of eleven different GPI-AP (CD14, CD16, CD24, CD48, CD52, CD58, CD59, CD66b, CD87, CD109 and CD157) during maturation of the neutrophil, monocytic, erythroid, lymphoid, basophil and plasmacytoid dendritic cells (DC) lineages in normal BM as a frame of reference for the understanding of the abnormal patterns of expression of GPI-AP observed in the BM of PNH patients.

Normal patterns of expression of glycosylphosphatidylinositol-anchored proteins on different subsets of peripheral blood cells: a frame of reference for the diagnosis of paroxysmal nocturnal hemoglobinuria.

Background: Evaluation of the expression of glycosylphosphatidylinositol-anchored membrane proteins (GPI-AP) is currently used for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). In this study, we analyzed the amount of expression of a wide variety of GPI-AP in different subsets of hematopoietic cells present in normal peripheral blood (PB), to establish their normal patterns of expression and provide a frame of reference for the definition of the best combination of GPI-AP and PB cell subsets to be applied in the diagnosis and monitoring of PNH.

Results: Our results show variable patterns of expression of different GPI-AP in distinct subsets of normal PB cells.

Comparative analysis of different flow cytometry-based immunophenotypic methods for the analysis of CD59 and CD55 expression on major peripheral blood cell subsets.

Background: Flow cytometry-based immunophenotypic techniques for the analysis of CD55 and CD59 expression on the major cell populations present in blood are the preferred method for the diagnostic screening of paroxysmal nocturnal hemoglobinuria (PNH).

Methods: In the present study, we comparatively analyze the effects of stain-lyse-and-then-wash techniques and lyse-wash-and-then-stain procedures on the detection of both CD55 and CD59 expression on the major peripheral blood (PB) leucocyte subsets, as analyzed by flow cytometry. Our major goal was to establish the minimum amounts of anti-CD55 and anti-CD59 reagents required to be added to a minimum volume of blood, which would allow an optimal staining for both antigens on red cells, platelets, and leucocytes present in a single tube.