CD36 cell surface expression as a surrogate marker to identify ABL/JAK-class kinase fusions in pediatric BCP-ALL.

Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with ABL-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations.

Red Blood Cell AE1/Band 3 Transports in Dominant Distal Renal Tubular Acidosis Patients.

Introduction: Anion exchanger 1 (AE1) ( gene product) is a membrane protein expressed in both kidney and red blood cells (RBCs): it exchanges extracellular bicarbonate (HCO ) for intracellular chloride (Cl) and participates in acid-base homeostasis. AE1 mutations in kidney α-intercalated cells can lead to distal renal tubular acidosis (dRTA). In RBC, AE1 (known as band 3) is also implicated in membrane stability: deletions can cause South Asian ovalocytosis (SAO).

Fetal cerebral hemorrhage due to X-linked GATA1 gene mutation.

We report a multiplex family with a GATA1 gene mutation responsible for a massive fetal cerebral hemorrhage occurring at 36 weeks. Two other stillbirth cousins presented with fetal hydrops and congenital hemochromatosis' phenotype at 37 and 12 weeks of gestation. Molecular screening revealed the presence of a c.

Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer.

Inherited red blood cell (RBC) membrane disorders, such as hereditary spherocytosis, elliptocytosis and hereditary ovalocytosis, result from mutations in genes encoding various RBC membrane and skeletal proteins. The RBC membrane, a composite structure composed of a lipid bilayer linked to a spectrin/actin-based membrane skeleton, confers upon the RBC unique features of deformability and mechanical stability. The disease severity is primarily dependent on the extent of membrane surface area loss.

A biomimetic microfluidic chip to study the circulation and mechanical retention of red blood cells in the spleen.

Red blood cells (RBCs) are deformable and flow through vessels narrower than their own size. Their deformability is most stringently challenged when they cross micrometer-wide slits in the spleen. In several inherited or acquired RBC disorders, blockade of small vessels by stiff RBCs can trigger organ damage, but a functional spleen is expected to clear these abnormal RBCs from the circulation before they induce such complications.

Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders.

Hereditary spherocytosis and elliptocytosis are the two most common inherited red cell membrane disorders resulting from mutations in genes encoding various red cell membrane and skeletal proteins. Red cell membrane, a composite structure composed of lipid bilayer linked to spectrin-based membrane skeleton is responsible for the unique features of flexibility and mechanical stability of the cell. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis.

Polymorphism in Gag gene cleavage sites of HIV-1 non-B subtype and virological outcome of a first-line lopinavir/ritonavir single drug regimen.

Virological failure on a boosted-protease inhibitor (PI/r) first-line triple combination is usually not associated with the detection of resistance mutations in the protease gene. Thus, other resistance pathways are being investigated. First-line PI/r monotherapy is the best model to investigate in vivo if the presence of mutations in the cleavage sites (CS) of gag gene prior to any antiretroviral treatment might influence PI/r efficacy.

X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI.

Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests.

Undetectable HIV-1 RNA load with the Cobas TaqMan v1.0 in a patient diagnosed at the time of primary HIV-1 infection.

Diagnosis of primary HIV-1 infection is challenging due to the presence of a serological window; thus, HIV-1-RNA quantitation and/or measurement of p24 antigenemia are recommended in such cases. A patient was diagnosed at the time of primary HIV-1 infection, he harbored a CFR02_AG subtype virus; quantitation of plasma HIV-1-RNA yielded an undetectable result according to one commercial assay, while HIV-1-RNA was detectable when measured with three other assays.

Low frequency of CXCR4-using viruses in patients at the time of primary non-subtype-B HIV-1 infection.

We used genotypic and phenotypic assays to estimate the frequency of X4/DM viruses in 131 patients infected with non-subtype-B viruses at the time of primary HIV-1 infection (PHI). All patients were enrolled in the French PRIMO Cohort from 1996 to 2007. Most strains belonged to CRF02_AG (51.

Short communication: evidence of HIV type 1 complex and second generation recombinant strains among patients infected in 1997-2007 in France: ANRS CO06 PRIMO Cohort.

Although subtype B strains are still predominant in France, non-B viruses have been isolated from 26% of patients with a primary HIV-1 infection in 2005-2006. The objective of this study was to characterize recombinant-HIV-1 strains by a subtyping based on the phylogenetic analysis of both pol and env sequences. We studied 591 patients who were part of the French PRIMO-Cohort between 1997 and 2007.

Despite being highly diverse, immunovirological status strongly correlates with clinical symptoms during primary HIV-1 infection: a cross-sectional study based on 674 patients enrolled in the ANRS CO 06 PRIMO cohort.

Objectives: To analyse immunovirological status during primary HIV-1 infection (PHI) according to contemporary clinical status and time since infection.

Methods: Plasma HIV-RNA and peripheral blood mononuclear cell (PBMC) HIV-DNA levels and CD4 cell counts were determined at enrolment in the ANRS PRIMO cohort. Time since infection was estimated based on both the number of antibodies on western blot at enrolment (0-1, 2-4 or > or =5 specific antibodies) and the estimated interval between infection and enrolment based on clinical and epidemiological features.

Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007).

Background: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality.

High frequency of X4/DM-tropic viruses in PBMC samples from patients with primary HIV-1 subtype-B infection in 1996-2007: the French ANRS CO06 PRIMO Cohort Study.

Objectives: To estimate the frequency of viruses with X4 or dual-X4/DM tropism from peripheral blood mononuclear cells (PBMCs) of 390 human immunodeficiency virus type 1 (HIV-1) subtype-B patients diagnosed at the time of primary HIV-1 infection (PHI) between 1996 and 2007 and enrolled in the PRIMO Cohort.

Methods: V3 loop sequences were amplified from HIV-1-DNA and analysed with a combination of five genotypic rules to predict tropism: (i) the '11/25 rule'; (ii) the net charge rule; (iii) the PSSM(X4/DM) algorithm; (iv) the PSSM(SI/NSI) algorithm; and (v) the SVM(Geno2pheno) algorithm.

Results: A high proportion (62/390, 15.

New and old complex recombinant HIV-1 strains among patients with primary infection in 1996-2006 in France: the French ANRS CO06 primo cohort study.

Background: Prevalence of HIV-1 non-B subtypes has increased overtime in patients diagnosed at the time of primary infection (PHI) in France. Our objective was to characterize in detail non-B strains which could not be genetically classified into the known subtypes/Circulating Recombinant Forms (CRFs).

Methods: Among 744 patients enrolled in the ANRS PRIMO Cohort since 1996, 176 (23.

HIV-1 DNA for the measurement of the HIV reservoir is predictive of disease progression in seroconverters whatever the mode of result expression is.

Background: HIV-1 DNA levels, reported as copies/10(6) peripheral blood mononuclear cells (PBMC), are very predictive of disease progression in seroconverters, independently of CD4(+)T cell count and HIV-RNA. Previously, HIV-DNA levels have sometimes been reported by other means: copies/10(6) CD4(+)T cells, reflecting the proportion of infected cells; or copies/mL whole blood, reflecting the global blood reservoir size.

Objectives: We investigated if the predictive value over the natural course of the disease depends on how the results are reported.

Absence of HIV-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine.

Background: New strategies such as boosted-protease inhibitor (PI) monotherapy are being investigated. However, a concern remains regarding the efficacy of this strategy in viral sanctuaries such as the male genital tract. More than 80% of untreated HIV-infected men have detectable HIV-RNA in semen and such a strategy could favour local selection of resistant variants, given the poor penetration of most PIs in semen.

Response to HAART in French patients with resistant HIV-1 treated at primary infection: ANRS Resistance Network.

Objective: The aim of the study was to analyse the response to highly active antiretroviral therapy (HAART) initiated at the time of primary HIV infection (PHI) in patients infected with a virus resistant to > or = 1 drug of their treatment compared with patients infected with a wild-type virus.

Methods: We analysed data from 350 patients who were enrolled from 1996-2004 in the French ANRS PRIMO Cohort or in the ANRS Resistance Group and treated with HAART during PHI. During the study period, HAART was initiated before the result of the genotypic resistance test was available.

Evaluation of cytomegalovirus (CMV) DNA quantification in dried blood spots: retrospective study of CMV congenital infection.

We compared two protocols for extracting DNA from dried blood spots for cytomegalovirus (CMV) DNA detection and quantification by real-time PCR. Both extraction methods were reliable for the retrospective diagnosis of CMV congenital infection. Quantification of CMV DNA was valuable after normalization of viral loads with albumin gene PCR amplification results.

Increase in hepatitis C virus incidence in HIV-1-infected patients followed up since primary infection.

Background: An increase in the incidence of sexually transmitted infections and hepatitis C virus (HCV) infections in HIV-infected men who have sex with men (MSM) has recently been reported.

Objective: To estimate HCV incidence and risk factors among HIV-1-infected patients followed up since primary HIV infection in the French PRIMO Cohort between 1996 and 2005.

Patients And Methods: All patients with at least 18 months of follow-up were studied.

Multicenter quality control of the detection of HIV-1 genome in semen before medically assisted procreation.

Couples in whom the man is HIV-1-positive may use medically assisted procreation in order to conceive a child without contaminating the female partner. But, before medically assisted procreation, the semen has to be processed to exclude HIV and tested for HIV nucleic acid before and after processing. The performance was evaluated of the technical protocols used to detect and quantify HIV-1 in 11 centers providing medically assisted procreation for couples with HIV-1 infected men by testing panels of seminal plasma and cells containing HIV-1 RNA and/or DNA.

HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time.

Objective: Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains.

Patients And Methods: Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients.

CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients.

Background: Treatment initiation at the time of primary human immunodeficiency virus (HIV) type 1 (HIV-1) infection has become less frequent in recent years.

Methods: In the French prospective PRIMO Cohort, in which patients are enrolled at the time of primary HIV-1 infection, 30% of the 552 patients recruited during 1996-2004 did not start receiving antiretroviral treatment during the first 3 months after diagnosis. We analyzed the patients' clinical and immunological outcomes and examined potential predictors of disease progression.

A virologic survey of patients admitted to a critical care unit for acute cardiorespiratory failure.

Objective: To document the prevalence of respiratory virus infections in patients with chronic cardiac or pulmonary disorders admitted to a critical care unit for acute cardiorespiratory failure.

Design, Setting, Patients: The study took place in a critical care unit during two consecutive winters. All patients admitted to the unit for acute respiratory or cardiac failure were enrolled.