COVID-19 inflammatory signature in a Mozambican cohort: unchanged red blood series and reduced levels of IL-6 and other proinflammatory cytokines.

Background: Alterations in haematological, biochemical parameters and cytokine levels, were reported in patients with COVID-19, however, there is an underrepresentation of the African population, which could provide evidence for understanding SARS-CoV-2 pathogenesis and useful tools for clinical management of cases. In this study, we aimed to determine the haematological, biochemical and cytokine profile in Mozambican individuals with SARS-CoV-2.

Methods: A cohort of 85 Mozambican individuals with RT-PCR SARS-CoV-2 results, was stratified into negative, asymptomatic, mild, moderate, and severe categories.

Multiparametric flow cytometry directing the evaluation of CRLF2 rearrangements and JAK2 status in pediatric B cell precursor acute lymphoblastic leukemia.

Introduction: This study aimed to determine whether cytokine receptor-like factor 2 (CRLF2) antigen expression evaluated using multiparametric flow cytometry (MFC) could predict the genotype of CRLF2 and Janus kinase 2 (JAK2) status for application in the diagnosis of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Methods: A total of 321 BCP-ALL bone marrow samples were collected, 291 at diagnosis and 13 at first relapse, while 17 samples were excluded due to low cellular viability. The CRLF2 antigen expression was evaluated using flow cytometry (percentage of positivity and median fluorescence intensity [MFI]).

Pediatric Acute Promyelocytic Leukemia: Epidemiology, Molecular Features, and Importance of GST-Theta 1 in Chemotherapy Response and Outcome.

Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among the geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering information from the population-based cancer registry (PBCR) and the diagnosis of APL obtained through incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to a loss of enzyme detoxification activity, possibly affecting the treatment response.

Corrigendum: The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia.

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The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages of T-cell differentiation arrest. We have revisited a cohort of pediatric T-ALL, in order to test if immunophenotypes associated with molecular alterations would predict the patient's outcome. Genetic mutations, translocations and copy number alterations were identified through Sanger sequencing, RT-PCR, FISH and multiplex ligation-dependent probe amplification (MLPA).

T-lymphoid/myeloid mixed phenotype acute leukemia and early T-cell precursor lymphoblastic leukemia similarities with mutation as a good prognostic factor.

T-lymphoid/Myeloid Mixed phenotype acute leukemia (T/M-MPAL) is ambiguous leukemia which overlaps with early T-cell precursor lymphoblastic leukemia (ETP-ALL). We have revisited the immunophenotyping profile of T/M-MPAL and ETP-ALL to identify differences and/or similarities, as these entities represent a therapeutic challenge in clinical practice. A total of 26 ETP-ALL and 10 T/M-MPAL cases were identified among 857 cases of childhood leukemia (T-ALL, n=266 and AML, n=591) before any treatment decisions.

CD9 predicts ETV6-RUNX1 in childhood B-cell precursor acute lymphoblastic leukemia.

Introduction: The ETV6-RUNX1 is a fusion gene associated with a good outcome in B-cell precursor lymphoblastic leukemia.

Objective: This study aimed to re-evaluate the CD9 cellular expression by flow cytometry (FC) as a possible tool to predict the presence of ETV6-RUNX1.

Method: Childhood B-cell precursor lymphoblastic leukemia cases were included (n=186).

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia.

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry.

Molecular Characterization of Pediatric Acute Myeloid Leukemia: Results of a Multicentric Study in Brazil.

Background And Aims: The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil.

Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia.

With the combination of immunophenotyping and molecular tests, it is still a challenge to identify the characteristics of T cell acute lymphoblastic leukemia (T-ALL) associated with distinct outcomes. This study tests the possible correlation of cellular expression of CD135 and CD117 with somatic gene mutations in T-ALL. One hundred sixty-two samples were tested, including 143 at diagnosis, 15 from T-lymphoblastic lymphoma at relapse, and four relapse samples from sequential follow-up of T-ALL.

Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children.

Copy number alterations (CNAs) in genes committed to B-cell precursors have been associated with poor survival in subgroups of patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We investigated submicroscopic alterations in a series of 274 Brazilian children with BCP-ALL by multiplex ligation-dependent probe amplification and evaluated their correlation with clinical and laboratory features. The relevance of overlapping CNA abnormalities was also explored.

Evaluation of multiplex ligation dependent probe amplification (MLPA) for identification of acute lymphoblastic leukemia with an intrachromosomal amplification of chromosome 21 (iAMP21) in a Brazilian population.

Background: An intrachromosomal amplification of chromosome 21 (iAMP21) defines a unique subgroup of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The finding of three or more extra copies of the RUNX1 gene by fluorescence in situ hybridization (FISH) is internationally used to define an iAMP21. Genomic profiling of chromosome 21 has been suggested for assisting diagnostic case identification.

EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus.

Adult thymuses lacking either ephrin type B receptor 2 (EphB2) or EphB3, or expressing a truncated form of EphB2, the forward signal-deficient EphB2LacZ, have low numbers of early thymic progenitors (ETPs) and are colonized in vivo by reduced numbers of injected bone marrow (BM) lineage-negative (Lin(-)) cells. Hematopoietic progenitors from these EphB mutants showed decreased capacities to colonize wild type (WT) thymuses compared with WT precursors, with EphB2(-/-) cells exhibiting the greatest reduction. WT BM Lin(-) cells also showed decreased colonizing capacity into mutant thymuses.

Inhibitory effects of Trypanosoma cruzi sialoglycoproteins on CD4+ T cells are associated with increased susceptibility to infection.

Background: The Trypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens characterized by decreased IL-2 synthesis. Trypanosoma cruzi mucin (Tc Muc) has been implicated in this phenomenom. These molecules contain a unique type of glycosylation consisting of several sialylated O-glycans linked to the protein backbone via N-acetylglucosamine residues.

Extrathymic CD4+CD8+ lymphocytes in Chagas disease: possible relationship with an immunoendocrine imbalance.

Double-positive (DP) CD4(+) CD8(+) T cells normally represent a thymic subpopulation that is developed in the thymus as a precursor of CD4(+) or CD8(+) single-positive T cells. Recent evidence has shown that DP cells with an activated phenotype can be tracked in secondary lymph organs. The detection of an activated DP population in the periphery, a population that expresses T cell receptors unselected during thymic negative selection in murine models of Trypanosoma cruzi infection and in humans with Chagas disease, raise new questions about the relevance of this population in the pathogenesis of this major parasitic disease and its possible link with immunoendocrine alterations.

Developing T-cell migration: role of semaphorins and ephrins.

Cell migration is a crucial event for normal T-cell development, and various ligand/receptor pairs have been implicated. Most of them, including chemokines and extracellular matrix proteins, have attractant properties on thymocytes. We discuss herein two further groups of ligand/receptor pairs, semaphorins/neuropilins and ephs/ephrins, which are constitutively expressed by thymocytes and thymic microenvironmental cells.

Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease.

Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery.

Is there a role for cellular prion protein in intrathymic T cell differentiation and migration?

The cellular prion protein (PrP(C)) is expressed in the nervous and immune systems. Functionally, PrP(C) has been suggested to participate in neuron survival, neuritogenesis and T lymphocyte activation. Moreover, PrP(C) interaction with laminin influences neuronal adhesion and neurite extension.