CD47 expression is decreased in hematopoietic progenitor cells in patients with myelofibrosis

Myelofibrosis (MF) is characterized by increased circulating hematopoietic progenitor cells (HPCs), abnormal cytokine levels, and the survival advantage of neoplastic progenitors over their normal counterparts, which leads to progressive disappearance of polyclonal hematopoiesis. CD47 is a surface glycoprotein with many functions, such as acting as a phagocytosis inhibitor of the expressing cell, that is increased in normal hematopoietic stem and progenitor cells mobilized into the blood and several human cancer-initiating cells, such as in acute myeloid leukemia. We compared CD47 expression in hematopoietic stem and progenitor cells of patients with MF and controls and found it to be decreased in progenitors of MF. Exposure of control HPCs to the cytokines transforming growth factor β and stromal-derived factor 1, which are important regulators of hematopoietic stem cell cycling and are overexpressed in patients with MF, did not modulate CD47 expression

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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

P>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 derivated from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8(+). The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed

Heart rate in fetuses and neonates in normal conditions and with mild depression

Peer Reviewe

Risk factors for mild depression in older women with overactive bladder syndrome-A cross sectional study.

BACKGROUND:Studies demonstrate an association between severe depression and overactive bladder syndrome (OAB). However, mild depression is constantly overlooked. The aim of this study was to evaluate the clinical and sociodemographic factors associated with mild depression in women with OAB. METHODS:Cross-sectional study involving 241 women over 60 years old in Brasilia, Brazil. All patients were subjected to an interview followed by questionnaires and physical examination. The clinical and sociodemographic variables analyzed were age, body mass index, physical activity level, OAB symptoms, presence of gynecological surgery, fecal incontinence, systemic arterial hypertension, Diabetes Mellitus, anxiety (Beck Anxiety Scale). The Geriatric Depression Scale-15 (GDS-15) was used to identify depression. Univariate logistic regression was used to assess the correlation between mild depression and the variables chosen. Variables with a p-value less than 0.2 were included in the multivariate logistic regression analysis. The level of confidence was set at 95%. RESULTS:121 volunteers suffered from mild depression. The multivariate analysis demonstrated that gynecological surgery (p < .001) and anxiety (p < .001) are factors associated with mild depression. Older women with a history of gynecological surgery and a GDS-15 score of 2.04 were 1.08 times more likely to develop mild depression compared to older women with no history of gynecological surgery. CONCLUSION:Anxiety and a history of gynecological surgery are factors that need to be taken into account and may influence the development of mild depression in older women with OAB. Psychological treatment should be considered an important adjunct in the treatment of women with symptoms of Overactive Bladder Syndrome

Results of FLT3 mutation screening and correlations with immunophenotyping in 169 Brazilian patients with acute myeloid leukemia

Univ São Paulo, Div Hematol, Dept Internal Med,Med Sch Ribeirao Preto, Natl Inst Sci & Technol Cell Based Therapy, BR-14049 Ribeirao Preto, BrazilUniv São Paulo, Dept Genet, Natl Inst Sci & Technol Cell Based Therapy, Med Sch Ribeirao Preto, BR-14048900 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Hematol & Hemotherapy, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Hematol & Hemotherapy, São Paulo, BrazilWeb of Scienc

The expression of Delta NTP73, 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 Delta Np73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and Delta NTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TATP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11, whereas higher Delta NTP73 expression was detected in non-RGA cases. TP53 expression did not vary according to Delta NTP73/TATP73 expression ratio. Leukaemic cells with higher Delta NTP73/TATP73 ratios were significantly more resistant to cytarabine-induced apoptosis