CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway

Re-Evaluation of Sinocastor (Rodentia: Castoridae) with Implications on the Origin of Modern Beavers

The extant beaver, Castor, has played an important role shaping landscapes and ecosystems in Eurasia and North America, yet the origins and early evolution of this lineage remain poorly understood. Here we use a geometric morphometric approach to help re-evaluate the phylogenetic affinities of a fossil skull from the Late Miocene of China. This specimen was originally considered Sinocastor, and later transferred to Castor. The aim of this study was to determine whether this form is an early member of Castor, or if it represents a lineage outside of Castor. The specimen was compared to 38 specimens of modern Castor (both C. canadensis and C. fiber) as well as fossil specimens of C. fiber (Pleistocene), C. californicus (Pliocene) and the early castorids Steneofiber eseri (early Miocene). The results show that the specimen falls outside the Castor morphospace and that compared to Castor, Sinocastor possesses a: 1) narrower post-orbital constriction, 2) anteroposteriorly shortened basioccipital depression, 3) shortened incisive foramen, 4) more posteriorly located palatine foramen, 5) longer rostrum, and 6) longer braincase. Also the specimen shows a much shallower basiocciptal depression than what is seen in living Castor, as well as prominently rooted molars. We conclude that Sinocastor is a valid genus. Given the prevalence of apparently primitive traits, Sinocastor might be a near relative of the lineage that gave rise to Castor, implying a possible Asiatic origin for Castor

Castor fiber plicidens (Rodentia, Mammalia) in the Late Villafranchian of Pietrafitta (Perugia, Central Italy)

In the lignite sediments of Pietrafitta (Tiberino Basin, Umbria, Central Italy), a rich fossil assemblage of vertebrate, invertebrate and plant remains belonging to the Farneta Faunal Unit (Late Villafranchian, Early Pleistocene) was collected. Among them fossil beaver cranial remains are relatively abundant. Western-Central Europe Villafranchian beaver remains were assigned to Castor plicidens by some authors because molar occlusal surface patterns show complex enamel crenulations. Several recent authors have classified them as C. fiber while analysing other morphological patterns. Our samples have been compared to Plio-Pleistocene fossil remains and to living European populations of the genus Castor. New morphometric parameters on molar occlusal surfaces have been defined and statistical analyses (One-Way MANOVA, Principal Component Analysis and Canonical Discriminant Analysis) have been performed on them. The results point out a subspecific separation between the Late Villafranchian beaver of Pietrafitta, Quarata and San Giovanni in Valdarno (Umbria and Tuscany) and C. fiber populations. St. Vallier (France) Late Pliocene and Mosbach 2 (Germany) Middle Pleistocene beavers classified respectively by Viret and Friant as C. plicidens, show a C. f. fiber molar teeth pattern. Therefore, C. fiber plicidens did not occur in Central-Western Europe and this subspecific name may be used only for the local populations of Valdarno and Tiberino Basin (San Giovanni in Valdarno, Quarata, Pietrafitta and a few localities of the same area), at that time peripheral populations, probably semi-isolated during the Late Villafranchian, and at the southern limit of the geographic range of C. fiber

Plio-PLeistocene evolution of the genus Castor (Rodentia, Mammalia) in Europe:C. fiber plicidens of Pietrafitta (Perugia, Central Italy).

In the lignite sediments of Pietrafitta (Tiberino Basin, Umbria, Central Italy), a rich fossil assemblage of vertebrate, invertebrate and plant remains belonging to the Farneta Faunal Unit (Late Villafranchian, Early Pleistocene) was collected. Among them fossil beaver cranial remains are relatively abundant. Western-Central Europe Villafranchian beaver remains were assigned to C. plicidens by some authors because molar occlusal surface patterns show complex enamel crenulations. Several recent authors have classified them as C. fiber while analysing other morphological patterns. Our samples have been compared to Plio-Pleistocene fossil remains and to living European populations of the genus Castor. New morphometric parameters on molar occlusal surfaces have been defined and statistical analyses (One-Way MANOVA, Principal Component Analysis and Canonical Discriminant Analysis) have been performed on them. The results point out a subspecific separation between the Late Villafranchian beaver of Pietrafitta, Quarata and San Giovanni in Valdarno (Umbria and Tuscany) and C. fiber populations. St. Vallier (France) Late Pliocene and Mosbach 2 (Germany) Middle Pleistocene beavers classified respectively by Viret and Friant as C. plicidens, show a C. f. fiber molar teeth pattern. Therefore, C. fiber plicidens did not occur in Central-Western Europe and this subspecific name may be used only for the local populations of Valdarno and Tiberino Basin (San Giovanni in Valdarno, Quarata, Pietrafitta and a few localities of the same area), at that time peripheral populations, probably semi-isolated during the Late Villafranchian, and at the southern limit of the geographic range of C. fiber

Addome acuto da rottura di feocromocitoma surrenalico

Il feocromocitoma è un tumore estremamente raro che si localizza nel 98% dei casi a livello del surrene; nelle forme familiari è sovente bilaterale. È presente in sindromi quali la MEN2, la sindrome di von Hippel-Lindau e la neurofibromatosi di tipo 1. Gli Autori descrivono il caso di una giovane donna con feocromocitoma del surrene di cospicue dimensioni ed esordio clinico con addome acuto, che ha richiesto un intervento di laparotomia esplorativa con adrenalectomica unilaterale. La terapia del feocromocitoma è chirurgica eventualmente associata nelle forme maligne (10%) a chemioterapia, radioterapia e trattamento con 131IMIBG (metaiodiobenzilguanidina marcata). In tutti i casi, mancando una correlazione tra aspetto microscopico e comportamento clinico, è necessario un follow-up attento e protratto nel tempo