FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase family member. Mutations in
, as well known, represent the most common genomic alteration in acute myeloid leukemia (AML), identified ...in approximately one-third of newly diagnosed adult patients. In recent years, this has represented an important therapeutic target. Drugs such as midostaurin, gilteritinib, and sorafenib, either alone in association with conventional chemotherapy, play a pivotal role in AML therapy with the mutated
gene. A current challenge lies in treating forms of AML with extramedullary localization. Here, we describe the general features of myeloid sarcoma and the ability of a targeted drug, i.e., gilteritinib, approved for relapsed or refractory disease, to induce remission of these extramedullary leukemic localizations in AML patients with
mutation, analyzing how in the literature, there is an important development of cases describing this promising potential for care.
In
Paracentrotus lividus embryos, a Mediterranean sea urchin species, HSP70 is present in all the cells. During cell division it localizes under normal growth conditions on the centrosomes and on the ...whole isolated mitotic apparatus. Now, in situ hybridization, Western blot analyses, and immunohistochemistry show that the HSP70 mRNA is present in both small and large
P. lividus oocytes, that all four isoforms of HSP70 can be found also in the oocytes, and that a certain amount of HSP70 localizes on asters and spindles during polar body formation. Moreover, two representative cell-cycle related proteins, cyclin B, and Cdc2, are present both in small and large oocytes, concentrating in the germinal vesicles before its breaking down. Cdc2 has been found in the cytoplasm of small oocytes and in the germinal vesicles of the large ones and then together with HSP70 on the mitotic apparatus of the dividing oocytes.
From the Department of Hematology and Bone Marrow Transplantation Unit, "V. Cervello" Hospital, Palermo, Italy (CA, FF, VR, LC, GC, AM, MLR, SM, AS); IFOM, Fondazione Istituto FIRC di Oncologia ...Molecolare, Milano, Italy (RB)
Correspondence: Alessandra Santoro, Laboratorio di, Ematologia, Divisione di Ematologia, e Unità Trapianti di Midollo Osseo, Ospedale V. Cervello, Via Trabucco, 180, 90146 Palermo, Italy. E-mail: santoro.al{at}libero.it
Although chromosomal abnormalities are detected by conventional cytogenetic analysis (CCA) in 40–60% of patients with acute myeloid leukemia (AML), cryptic chromosomal deletions may only be detected by molecular analysis. To determine their frequency, we studied 74 cases of AML by microsatellite allelotype assay using 35 microsatellites spanning eight chromosomal regions known to be frequently involved in AML. In 42 (57%) we found DNA imbalance at the screened loci. This was detected by CCA only in 4 cases. Our data show that cryptic deletions are a common event in AML.
Key words: LOH, acute leukemia, recurrent chromosomal aberrations.
The American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) have been ...recently strongly recommended the evaluation of mismatch repair status (MMS) as molecular biomarkers in colorectal cancer for a better prognostic stratification of patients. This recommendation is emphasized by the recent evidence of Microsatellite Instability (MSI) as a predictive marker for chemotherapy and immunotherapy.
In this scenario, the validation of molecular biomarker testing methods seems to be essential to design the most appropriate tailored therapy and the most suitable care strategy, respectively.
In this study, we validated an alternative method based on capillary electrophoresis system label-free PCR (Qiaxcel system) to evaluate the MSI Bethesda Panel. We also parallel the results with a standard approach.
Our data showed total concordance with the standard approach, with a highly time-efficient and easy procedure combined with high sensitivity for MSI detection.
Alternative capillary electrophoresis based on label-free PCR such as the Qiaxel system is a very sensitive and specific method to detect MSI for the management of patients with colorectal cancer. This procedure is adequate and suitable in diagnostic routine for the evaluation of microsatellite repeats compared to standard procedures.
Highlights • Generation of miR-155 network on FLT3-ITD+ AML utilizing data from multiple sources. • Connections among miR-155 and master myeloid transcription factor in FLT3-ITD+ AML. • Inhibition of ...FLT3-ITD decreases p-JUN and miR-155 and increases miR-155 targets. • Inverse correlation between miR-155 and TFs (PU.1 and CEBP-beta) in FLT3-ITD+ AML. • In vitro functional experiments of miR-155 mimic and silencing confirm our model.
Abstract The objective of this study was to identify the endometrial gene expression profile in receptive phase, which could represent a useful prognostic tool for selecting IVF patients. Endometrial ...expression of 47 selected genes biopsied during the window of implantation in natural cycles was compared between patients who achieved a successful pregnancy spontaneously or after subsequent intracytoplasmic sperm injection (ICSI) cycles and patients who did not achieve a pregnancy after at least two failed ICSI cycles. The comparative analysis showed significantly different levels of expression in 19 genes, five implicated in apoptosis ( CASP8 , FADD , CASP10 , APAF1 , ANXA4 ), three in immunity ( LIF , SPP1 , C4BPA ), five in transcriptional activity ( MSX1 , HOXA10 , MSX2 , HOXA11 , GATA2 ), two in lipid metabolism ( LEPR , APOD ) and four in oxidative metabolism ( AOX1 , ALDH1A3 , GPX3 , NNMT ). The evidence for these genes being differently expressed could represent the starting point of identifying the ideal receptive endometrial gene expression profile, which could be used in the future as a prognostic tool for IVF patients. Gene expression analysis technology has opened new important perspectives on the study of the physiological processes of different tissues and organs. Specifically for the endometrium, it would be really interesting to find out an endometrial gene expression profile of receptive phase, which could be used in future as a useful prognostic tool for selecting IVF patients. To achieve this aim, the objective of the present paper was the comparison of endometrial expression in natural cycles of 47 selected genes between the biopsies of patients who achieved a successful pregnancy, either spontaneously or after subsequent ICSI cycles, and those of patients who did not achieve a pregnancy after at least two failed ICSI cycles. The comparative analysis showed a significant different expression in 19 genes: five implicated in programmed cell death, known as apoptosis ( CASP8 , FADD , CASP10 , APAF1 , ANXA4 ), three in immunity ( LIF , SPP1 , C4BPA ), five in transcriptional activity ( MSX1 , HOXA10 , MSX2 , HOXA11 , GATA2 ), two in lipid metabolism ( LEPR , APOD ) and four in oxidative metabolism ( AOX1 , ALDH1A3 , GPX3 , NNMT ). The evidence of these genes being differently expressed could represent the starting point of identifying the ideal receptive endometrial gene expression profile which could be used in the future as a prognostic tool for IVF patients.
In the present study, double immunofluorescence and immunoblot analysis have been used to show that centrosomes, isolated from Paracentrotus lividus sea urchin embryos at the first mitotic metaphase, ...contain the constitutive chaperone, heat-shock protein (HSP) 70. More specifically, we demonstrate that centrosomes contain only the HSP70-d isoform, which is one of the four isoforms identified in P. lividus. We also provide evidence that p34(cell division control kinase-2) and t complex polypeptide-1 (TCP-1) alpha, a subunit of the TCP-1 complex, are localized on the centrosomes. Furthermore, inhibition of TCP-1 in vivo, via microinjecting an anti-(TCP-1 alpha) antibody into P. lividus eggs before fertilization, either impaired mitosis or induced severe malformations in more than 50% of embryos. In addition, we have isolated the whole mitotic apparatus and shown that HSP70 localizes on the fibres of spindles and asters, and binds them in an ATP-dependent manner. These observations suggest that HSP70 has a chaperone role in assisting the TCP-1 complex in tubulin folding, when localized on centrosomes, and during the assembling and disassembling of the mitotic apparatus, when localized on the fibres of spindles and asters.
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