Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

Background: Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34(+) hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters. Results: By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34(+) cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34(+) cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro-apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly. Conclusions: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.

A new dic(7;12)(p12.21;p12.2) and i(12)(q10) during the lymphoid blast crisis of patient with Ph plus chronic myeloid leukemia

Chronic myelogenous leukemia (CML) is a common myeloproliferative disease that is characterized by the clonal expansion of marrow stem cells, and is associated with the Philadelphia chromosome. As the disease progresses, additional chromosome abnormalities may arise. The prognostic impact of secondary chromosomal abnormalities in CML is complex, heterogeneous, and sometimes related to previous treatment. Here, we describe a CML patient in lymphoid blast crisis associated with a new chromosomal abnormality identified, dic(7;12)(p12.21;p12.2) and i(12)(q10) using classical cytogenetics and spectral karyotype analysis. To the best of our knowledge, this is the first report of t(7;12)(p11.1;q11.1) and i(12)(q10) in a CML patient with lymphoid evolution.

Risks, Benefits, and Therapeutic Potential of Hematopoietic Stem Cell Transplantation for Autoimmune Diabetes

Type 1 diabetes mellitus is a chronic disease that results from the autoimmune response against pancreatic insulin producing beta cells. Apart of several insulin regimens, since the decade of 80s various immunomodulatory regimens were tested aiming at blocking some steps of the autoimmune process against beta cell mass and at promoting beta cell preservation. In the last years, some independent research groups tried to cure type 1 diabetes with an "immunologic reset" provided by autologous hematopoietic stem cell transplantation in newly diagnosed patients, and the majority of patients became free form insulin with increasing levels of C-peptide along the time. In this review, we discuss the biology of hematopoietic stem cells and the possible advantages and disadvantages related to the high dose immunosuppression followed by autologous hematopoietic stem cell transplantation.

Famílias incestuais

A autora se propõe examinar uma configuração familiar que nomeia, a partir da conceituação de Racamier (1995), de família incestual e que se caracteriza por relações internas que negam as diferenças entre os sexos e entre as gerações. Propõe que esta configuração ressoa, no interior da família, aspectos da vida social na contemporaneidade, tais como descritos por diversos autores, dentre eles Baudrillard (2009). Apresenta um caso clínico que serve para ilustrar aspectos do funcionamento psíquico de uma família incestual.

Sobre o campo da Psicologia Social

O campo da Psicologia Social é apresentado como território fértil, na contemporaneidade, para constituir-se como um laboratório para a produção em Ciências Humanas, uma vez que, no século XX, cada vez mais o social foi em direção ao psicológico. Neste campo, nosso embate dá-se no modo como entendemos o hífen pressuposto na integração psicossocial. A autora propõe que, entre o psicológico e o social, o hífen domina, pois ele é a própria essência relacional que é inerente a cada um dos elementos. Sugere que o modelo para entender o homem e suas circunstâncias proposto por Freud imbrica de forma indissociável o psicológico e o social, a ontogênese e a filogênese, com uma potência que teve impacto sobre todo o campo das Ciências Humanas. A Psicanálise é um instrumento hermenêutico para colaborar na elucidação dos fenômenos sociais. A autora utiliza imagens construídas por Freud e Walter Benjamin e poemas de Carlos Drummond de Andrade para fortalecer o entendimento do hífen psicossocial tanto em sua ação multidimensional quanto em sua organização.