Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by a block in differentiation and accumulation of promyelocytes in the bone marrow and blood. The majority of APL patients harbor the t(15:17) translocation leading to expression of the fusion protein promyelocytic-retinoic acid receptor alpha. Treatment with retinoic acid leads to degradation of promyelocytic-retinoic acid receptor alpha protein and disappearance of leukemic cells; however, 30% of APL patients relapse after treatment.

Monoclonal B-cell lymphocytosis in first-degree relatives of patients with sporadic (non-familial) chronic lymphocytic leukaemia.

Although biological similarities have been described among monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukaemia (CLL), the relationships between these two conditions are not fully understood, and new epidemiological studies in different populations and different countries continue to be reported. Here, we investigated 167 first-degree relatives from 42 families of patients with non-familial (sporadic) CLL, using four-colour flow cytometry. MBL was found in seven of 167 subjects (4.

The presence of CD56/CD16 in T-cell acute lymphoblastic leukaemia correlates with the expression of cytotoxic molecules and is associated with worse response to treatment.

Some cases of T-cell acute lymphoblastic leukaemia (ALL) express markers found in natural-killer (NK) cells, such as CD56 and CD16. Out of 84 T-cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28.5%), which we designated T/NK-ALL group.

Apoptosis induction by (+)alpha-tocopheryl succinate in the absence or presence of all-trans retinoic acid and arsenic trioxide in NB4, NB4-R2 and primary APL cells.

We analyzed the effect of (+)alpha-tocopheryl succinate (alpha-TOS) alone or associated with arsenic trioxide (ATO) or all-trans retinoid acid (ATRA) in acute promyelocytic leukemia (APL). alpha-TOS-induced apoptosis in APL clinical samples and in ATRA-sensitive (NB4) and ATRA-resistant (NB4-R2) APL cell lines. The effective dose 50% (ED-50) was calculated to be 71 and 58muM, for NB4 and NB4-R2, respectively.

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency.

The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA. Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Emu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed.

Effects of ultrasound on the proliferation and differentiation of cementoblast lineage cells.

Background: The purpose of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) stimulation on the proliferation and differentiation of cementoblast lineage cells.

Methods: An immortalized human periodontal ligament cell line (HPL) showing immature cementoblastic differentiation was used. Cultured HPL cells were subjected to LIPUS exposure (frequency = 1 MHz; pulsed 1:4; intensity = 30 mW/cm(2)) or sham exposure for 15 minutes per day.

The expression of DeltaNTP73, TATP73 and TP53 genes in acute myeloid leukaemia is associated with recurrent cytogenetic abnormalities and in vitro susceptibility to cytarabine cytotoxicity.

TP73 encodes for two proteins: full-length TAp73 and DeltaNp73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and DeltaNTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells.

[From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia].

Acute promyelocytic leukemia (APL) is a model of clinical applicability of the knowledge of molecular physiopathology. It is characterized by recurrent genetic involvement of the retinoic acid alpha receptor. The consequence is a protein with low sensibility to its ligand and a myeloid maturation arrest.

Translocations t(X;14)(q28;q11) and t(Y;14)(q12;q11) in T-cell prolymphocytic leukemia.

We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derived from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8+.

Dynamic shear behavior of mandibular condylar cartilage is dependent on testing direction.

Little information is available on the direction-dependency of shear behavior in mandibular condylar cartilage. Therefore, we tested the hypothesis that such a dependency of the dynamic shear properties is present in mandibular condylar cartilage. From each of 17 condyles, two cartilage-bone plugs were dissected and tested in a simple shear sandwich configuration under a compressive strain of 10%.

Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia.

Background: The most primitive leukemic precursor in acute myeloid leukemia (AML) is thought to be the leukemic stem cell (LSC), which retains the properties of self-renewal and high proliferative capacity and quiescence of the hematopoietic stem cell. LSC seems to be immunophenotypically distinct and more resistant to chemotherapy than the more committed blasts. Considering that the multidrug resistance (MDR) constitutive expression may be a barrier to therapy in AML, we have investigated whether various MDR transporters were differentially expressed at the protein level by different leukemic subsets.

Adhesion molecules and Differentiation Syndrome: phenotypic and functional analysis of the effect of ATRA, As2O3, phenylbutyrate, and G-CSF in acute promyelocytic leukemia.

Background And Objectives: Differentiation Syndrome (DS) is a treatment complication which can occur in patients treated with acute promyelocytic leukemia (APL) with all transretinoic acid (ATRA) or As(2)O(3), and is characterized by enhanced leukocyte transmigration. As(2)O(3), Phenylbutyrate (PB) and G-CSF are known to potentiate ATRA effects. Our aim was to analyze the changes in expression and function of adhesion molecules induced by ATRA, As(2)O(3), G-CSF and PB, and their association.

Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines.

We report an increased incidence of high relapse risk features in 157 APL Brazilian patients. Out of 134 patients treated with ATRA and anthracyclines, only 91 (67.9%) achieved remission because 43 (32%) died during induction.

PAHs and BTEX in groundwater of gasoline stations from Rio de Janeiro City, Brazil.

PAHs and BTEX were studied in groundwater from monitoring wells of gasoline stations of Rio de Janeiro City, Brazil during 2003 and 2004. Total PAH concentration ranged from 0.05 to 84.

Shear bond strength of metallic brackets photo-activated with light-emitting diode (LED) at different exposure times.

The purpose of this study was to compare the shear bond strength of orthodontic metallic brackets photo-activated with two different light-curing sources at different exposure times: halogen light (XL 1500, 3M ESPE) and LED light (Ortholux, 3M Unitek). Sixty bovine permanent lower incisors were inserted into PVC tubes containing plaster. The buccal surfaces were cleaned with pumice and water, and then etched with 37% phosphoric acid gel.

The association of ICAM-1 Exon 6 (E469K) but not of ICAM-1 Exon 4 (G241R) and PECAM-1 Exon 3 (L125V) polymorphisms with the development of differentiation syndrome in acute promyelocytic leukemia.

The use of all trans-retinoic acid (ATRA) is the basis of treatment of acute promyelocytic leukemia (APL) and represents the paradigm of differentiation therapy. In general, ATRA is well-tolerated but may be associated with a potentially lethal side-effect, referred to as retinoic acid or differentiation syndrome (DS). The cellular and molecular mechanisms of DS are poorly understood and involve changes in the adhesive qualities and cytokine secretion of leukemic cells during ATRA-induced differentiation.

Biomechanical response of condylar cartilage-on-bone to dynamic shear.

Shear stress can result in fatigue, damage, and irreversible deformation of the mandibular condylar cartilage. However, little information is available on its dynamic properties in shear. We tested the hypothesis that the dynamic shear properties of the condylar cartilage depend on the frequency and amplitude of shear strain.

Flow cytometry characterization of leukemic phase of nasal NK/T-cell lymphoma in tumor biopsies and peripheral blood.

We report the findings of the immunophenotypic profile of three cases of nasal T/NK cell lymphoma in leukemic phase. Flow cytometry analysis was carried out using cell suspensions of tumor nasal biopsies and peripheral blood. Tumor samples were composed by a mixture of a predominant subset of medium-size true NK cytCD3epsilon-, sCD3epsilon-, CD56+ cells mixed with a minor subset of medium-size T/NK sCD3epsilon+, CD56+ cells.

Acute myeloid leukemia (AML-M2) with t(5;11)(q35;q13) and normal expression of cyclin D1.

We report a case of acute myeloid leukemia (AML) subtype M2, with t(5;11)(q35;q13), in a 30-year-old man. Conventional cytogenetic, spectral karyotyping, and fluorescence in situ hybridization (FISH) studies on bone marrow sample obtained at diagnosis revealed an abnormal karyotype in all cells examined. FISH analysis demonstrated absence of translocations in the region of the cyclin D1 gene and real-time quantitative reverse transcriptase-polymerase chain reaction revealed normal expression of this gene.

Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration.

Acute promyelocytic leukemia (APL), a relatively rare hematologic malignancy, is highly curable with current treatment strategies. However, these strategies may be unavailable in countries with limited resources. A review of records in several Latin American countries revealed that approximately 30% of deaths among children and adults with APL were caused by early complications associated with the disease or its treatment.

Comparison of dynamic shear properties of the porcine molar and incisor periodontal ligament.

The role of the periodontal ligament (PDL) is to support the tooth during function and resist external forces applied to it. The dominant vertical component of these forces is associated with shear in the PDL. The mechanical response to vertical force may, however, be different between the molar and incisor as their loading regimen is different.

Anti-inflammatory effects of atorvastatin: modulation by the T-786C polymorphism in the endothelial nitric oxide synthase gene.

Statins produce cholesterol-independent, anti-inflammatory effects, which result at least in part from increased endothelial nitric oxide production. These effects may be modulated by polymorphisms in the endothelial nitric oxide synthase (eNOS) gene. Here, we examined whether the T-786C polymorphism of eNOS gene affects the concentrations of markers of atherosclerosis and inflammation (sCD40L, sVCAM-1, sICAM-1, sP-selectin, MCP-1, high sensitivity (hs)-CRP, MMP-2, MMP-9, and TIMP-1).

Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita.

The DKC1 gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA). DKC1 is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations in ribosome modification might lead to cancer and other features of the disease remains unknown.

Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha transgenic mouse model.

Acute promyelocytic leukemia (APL) is characterized by the expansion of blasts that resemble morphologically promyelocytes and harbor a chromosomal translocation involving the retinoic acid receptor alpha (RARalpha) and the promyelocytic leukemia (PML) genes on chromosomes 17 and 15, respectively. The expression of the PML/RARalpha fusion gene is essential for APL genesis. In fact, transgenic mice (TM) expressing PML/RARalpha develop a form of leukemia that mimics the hematological findings of human APL.