CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / HematogÃnias sÃo cÃlulas jovens normais da medula Ãssea responsÃveis pela produÃÃo das cÃlulas de linhagem B do sistema imunolÃgico. A leucemia linfoblÃstica aguda de cÃlulas precursoras B representa um dos tipos de transformaÃÃo neoplÃsica das hematogÃnias. Devido a alta similaridade do ponto de vista citolÃgico dos dois tipos celulares, à possÃvel haver erros de interpretaÃÃo na anÃlise citolÃgica, fazendo-se necessÃrio em algumas circunstÃncias o uso de tÃcnicas complementares diagnÃsticas para diferenciar as cÃlulas benignas das malignas. O uso de marcadores imunolÃgicos atravÃs de anticorpos monoclonais marcados com fluorescÃncia tem grande aplicabilidade nos laboratÃrios especializados como rotina no estudo das leucemias. Os antÃgenos CD10 e CD19 estÃo expressos em ambos os tipos celulares de forma que se faz necessÃria uma extensÃo no uso de outros marcadores para caracterizaÃÃo da natureza benigna ou maligna das cÃlulas. Testou-se possÃveis diferenÃas nas curvas de expressÃo de CD10 e CD19 dos dois tipos celulares. Foram colhidas 36 amostras de medula Ãssea de pacientes pediÃtricos nÃo neoplÃsicos como grupo controle. A idade variou de 24 dias de vida a 15 anos com uma mÃdia de 5 anos. Foram colhidas tambÃm 39 amostras de pacientes portadores de LLA de linhagem B por ocasiÃo do diagnÃstico. A idade variou de 4 meses a 14 anos com uma mÃdia de 6,6 anos. Analisou-se as diferenÃas nas distribuiÃÃes quanto a intensidade de fluorescÃncia pelas mÃdias, desvios-padrÃo, coeficientes de variaÃÃo, coeficientes de inclinaÃÃo e coeficiente de curtose para os dois marcadores CD10 e CD19 nos dois grupos. Os valores individuais de cada amostra foram comparados com os intervalos gerados pelos valores do grupo controle com os seguintes respectivos resultados de sensibilidade e especificidade: 89,7% e 75% para um cut-off de mÃdia+2DP; 79,5% e 100% para mÃdia+2,5DP; e 71,8% e 100% para mÃdia+3DP. ConclusÃo: A expressÃo de CD10 e CD19 em blastos e hematogÃnias à diferente podendo ser de utilidade prÃtica na distinÃÃo entre os dois tipos celulares. / Hematogones are normal immature cells from bone marrow that are responsible for the production of the immune systemâs B cell lineage. The acute lymphoblastic leukemia (ALL) of precursors B cells represents one type of neoplastic transformation of hematogones. Due to their high similarity there are risks of erroneous interpretation consequently making it necessary use to complementary diagnostic techniques. The CD10 and CD19 antigens are expressed on both types of cells so, it is necessary use other monoclonal antibodies to identify malign or benign nature. In attempt to avoid the use of different antibodies we investigate possible differences in the expression of CD10 and CD19 in both cell types. We collected 36 samples of bone marrow from non-neoplastic patients as a control group. The age raged from 0 to 15 years with an average of 5 years. It was also collected 39 samples from patients with ALL of B cells. The age ranged from 0 to 14 years with an average of 6.6 years. We analyzed the differences between the fluorescence intensity concerning average, standard deviation, variation, inclination and kurtosis coefficients for the two markers. The individual values of each sample were compared with the intervals generated by the values of the control group: MEÂ2SD; MEÂ2.5SD and MEÂ3SD. It was possible to distinguish the groups with 89.7% and 75%; 79.5% and 100% and 71.8% e 100% of sensibility and specificity, respectively for the intervals. In conclusion, the expression of CD10 and CD19 antigens on blasts and hematogones is significantly different and may be useful in the differentiation of both cell types

Bakgrund: Akut lymfatisk leukemi (ALL) är den vanligaste cancerformen bland barn och ungdomar och kan innebära stor fysisk och psykisk påfrestning hos föräldrar och barn. När barnet drabbas av ALL kan föräldrar känna oro och rädsla för att förlora barnet. Syfte: Syftet med studien var att belysa föräldrars upplevelser när barnet har drabbats av akut lymfatisk leukemi (ALL). Metod: En litteraturstudie med induktiv ansats genomfördes där elva artiklar granskades och valdes till resultat. Resultat: I resultatet framkom huvudkategorin: Upplevelse av att vara förälder till barn som drabbats av ALL med underkategorier: att känna livet krascha, att känna otillräcklighet, att oroas över ekonomin, att känna behov av förändrade föräldrastrategier och att blicka framåt. Andra huvudkategorin var Upplevelse av sjuksköterskans betydelse med underkategorier: att känna emotionellt stöd och att uppleva behov av information och undervisning. Föräldrar upplevde kommunikation med sjuksköterska som viktigt och hjälpte föräldrar hantera påfrestningen. Vid bristande kommunikation upplevde föräldrar att sjuksköterskan undanhöll information och tilliten till sjuksköterskan försvann. Slutsats: Studien kan ge kunskap om föräldrars upplevelser när barnet drabbas av ALL och vilka behov som finns av hjälp och stöd. Mer forskning krävs för att undersöka på vilket sätt sjuksköterskan kan underlätta för föräldrar under den påfrestande tiden. / Background: Acute lymphocytic leukemia (ALL) is the most common cancer in children and youth and may cause great physical and psychological burden on parents and children. Parents might worry and fear losing the child when their child has ALL. Aim: The aim of this study was to explore parent's experiences when their child suffered from acute lymphocytic leukemia (ALL). Method: A literature review with an inductive structure was performed where eleven articles were analyzed and chosen for results. Result: The result presents main category: Experience of being a parent off a child affected by ALL with subcategories: to feel life crashing, to feel insufficient, to worry about economics, to feel the need of changing parent strategies, to focus ahead. The second main category was The experience of the importance of the nurse with subcategories: to feel emotional support and to experience the need for information and education. Parents experienced that communication with the nurse was important and helped parents manage burden. Lack of communication made parents experience that the nurse withheld information and the trust disappeared. Conclusions: The study can provide knowledge about parent's experiences when their child has ALL and the need of help and support. More research is required to investigate in which way the nurse can ease parent's burden during the stressful time.

Le dihydrofolate réductase (DHFR) est la principale cible du méthotrexate, un important composant du traitement de la leucémie lymphoblastique aiguë (LLA). Une association des polymorphismes du promoteur de DHFR avec l’issue de la LLA a été mise en évidence au laboratoire. Une survie sans événement (EFS) réduite corrélait avec les allèles A -317 et C -1610, et l’haplotype *1, défini par ces allèles. L’haplotype *1 était aussi associé à une expression élevée du DHFR. Dans cette étude, nous étendons l’analyse à la région régulatrice adjacente, d’environ 400 pb, correspondant au transcrit mineur non-codant du DHFR, qui joue un rôle essentiel dans la régulation de la transcription au niveau du promoteur majeur. Six polymorphismes ont été identifiés, parmi lesquels 5 étaient des SNPs et un polymorphisme de longueur composé d’un nombre variable d’éléments de 9 pb et d’une insertion/délétion de 9 pb. L’analyse d’haplotype, incluant tous les polymorphismes promoteurs, a révélé une diversification de l’haploytpe *1 en 5 sous-types (*1a à *1e). Les variations du promoteur majeur et les sous-types de l’haplotype *1 ont été par la suite analysés pour l’association avec l’issue de LLA. Un EFS réduit corrélait avec l’allèle A du polymorphisme G308A (p=0,02) et avec l’haplotype *1 (p=0,01). Des niveaux élevées d’ARNm étaient trouvés chez les porteurs de l’haplotype *1b (p=0,005) et pas pour les autres sous-types de l’haplotype *1. Alors, la mauvaise issue de LLA associée avec l'haplotype *1 est en effet déterminée par le sous-type *1b. Cette étude donne un nouvel aperçu des polymorphismes régulateurs du DHFR définissant plus précisément les variations du DHFR prédisposant un événement. / Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. We recently reported an association of DHFR promoter polymorphisms with ALL outcome. Lower event free survival (EFS) correlated with the alleles A -317 and C -1610, and with haplotype *1, defined by these alleles. Haplotype*1 was also associated higher DHFR expression. Here we extended the analysis to adjacent 400bp regulatory region corresponding to non-coding minor DHFR transcript which plays an essential role in the regulation of transcription from the major promoter. Six polymorphisms were identified, of which 5 were SNPs and one length polymorphism composed of variable number of 9bp elements and 9bp insertion/deletion. Haplotype analysis including all promoter polymorphisms revealed diversification of haplotype *1 into 5 subtypes (*1a to *1e). Major promoter variations and haplotype *1 subtypes were subsequently analyzed for the association with ALL outcome. Lower EFS correlated with an A allele of G308A polymorphism (p=0.02) and with *1b haplotype (p=0.01). Higher mRNA levels were found in the carriers of *1b haplotype (p=0.005) and not for remaining haplotype *1 subtypes. So, the worse ALL outcome associated with haplotype *1 is actually determined by the subtype *1b. The study provides a new insight into DHFR regulatory polymorphisms defining more precisely event–predisposing DHFR variations.

Le dihydrofolate réductase (DHFR) est la principale cible du méthotrexate, un important composant du traitement de la leucémie lymphoblastique aiguë (LLA). Une association des polymorphismes du promoteur de DHFR avec l’issue de la LLA a été mise en évidence au laboratoire. Une survie sans événement (EFS) réduite corrélait avec les allèles A -317 et C -1610, et l’haplotype *1, défini par ces allèles. L’haplotype *1 était aussi associé à une expression élevée du DHFR. Dans cette étude, nous étendons l’analyse à la région régulatrice adjacente, d’environ 400 pb, correspondant au transcrit mineur non-codant du DHFR, qui joue un rôle essentiel dans la régulation de la transcription au niveau du promoteur majeur. Six polymorphismes ont été identifiés, parmi lesquels 5 étaient des SNPs et un polymorphisme de longueur composé d’un nombre variable d’éléments de 9 pb et d’une insertion/délétion de 9 pb. L’analyse d’haplotype, incluant tous les polymorphismes promoteurs, a révélé une diversification de l’haploytpe *1 en 5 sous-types (*1a à *1e). Les variations du promoteur majeur et les sous-types de l’haplotype *1 ont été par la suite analysés pour l’association avec l’issue de LLA. Un EFS réduit corrélait avec l’allèle A du polymorphisme G308A (p=0,02) et avec l’haplotype *1 (p=0,01). Des niveaux élevées d’ARNm étaient trouvés chez les porteurs de l’haplotype *1b (p=0,005) et pas pour les autres sous-types de l’haplotype *1. Alors, la mauvaise issue de LLA associée avec l'haplotype *1 est en effet déterminée par le sous-type *1b. Cette étude donne un nouvel aperçu des polymorphismes régulateurs du DHFR définissant plus précisément les variations du DHFR prédisposant un événement. / Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. We recently reported an association of DHFR promoter polymorphisms with ALL outcome. Lower event free survival (EFS) correlated with the alleles A -317 and C -1610, and with haplotype *1, defined by these alleles. Haplotype*1 was also associated higher DHFR expression. Here we extended the analysis to adjacent 400bp regulatory region corresponding to non-coding minor DHFR transcript which plays an essential role in the regulation of transcription from the major promoter. Six polymorphisms were identified, of which 5 were SNPs and one length polymorphism composed of variable number of 9bp elements and 9bp insertion/deletion. Haplotype analysis including all promoter polymorphisms revealed diversification of haplotype *1 into 5 subtypes (*1a to *1e). Major promoter variations and haplotype *1 subtypes were subsequently analyzed for the association with ALL outcome. Lower EFS correlated with an A allele of G308A polymorphism (p=0.02) and with *1b haplotype (p=0.01). Higher mRNA levels were found in the carriers of *1b haplotype (p=0.005) and not for remaining haplotype *1 subtypes. So, the worse ALL outcome associated with haplotype *1 is actually determined by the subtype *1b. The study provides a new insight into DHFR regulatory polymorphisms defining more precisely event–predisposing DHFR variations.