The acute myeloid leukemia associated AML1-ETO fusion protein alters the transcriptome and cellular progression in a single-oncogene expressing in vitro induced pluripotent stem cell based granulocyte differentiation model

Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect normal hematopoiesis. The analysis of human AMLs has mostly been performed using end-point materials, such as cell lines and patient derived AMLs that also carry additional contributing mutations. The molecular effects of a single oncogenic hit, such as expression of the AML associated oncoprotein AML1-ETO on hematopoietic development and transformation into a (pre-) leukemic state still needs further investigation. Here we describe the development and characterization of an induced pluripotent stem cell (iPSC) system that allows in vitro differentiation towards different mature myeloid cell types such as monocytes and granulocytes. During in vitro differentiation we expressed the AML1-ETO fusion protein and examined the effects of the oncoprotein on differentiation and the underlying alterations in the gene program at 8 different time points. Our analysis revealed that AML1-ETO as a single oncogenic hit in a non-mutated background blocks granulocytic differentiation, deregulates the gene program via altering the acetylome of the differentiating granulocytic cells, and induces t(8;21) AML associated leukemic characteristics. Together, these results reveal that inducible oncogene expression during in vitro differentiation of iPS cells provides a valuable platform for analysis of aberrant regulation in disease

Predicting the extent of nodal involvement for node positive breast cancer patients: Development and validation of a novel tool

Background: This study aimed to develop an easy to use prediction model to predict the risk of havin

Donor Site Satisfaction Following Autologous Fat Transfer for Total Breast Reconstruction

BACKGROUND: With evolving breast cancer survival and patient preferences, it is essential that reconstructive surgeons worldwide keep searching for the best reconstruction technique for patients. Autologous fat transfer (AFT) is a relatively new technique for total breast reconstruction that has already proven to be effective and safe with all advantages of autologous tissue. However, little is known about aesthetic results and satisfaction concerning donor sites. OBJECTIVES: The aim of this study was to measure donor site satisfaction following AFT for total breast reconstruction in breast cancer patients. METHODS: Between May and August of 2021, participants of the BREAST- trial who were at least 24 months after their final reconstruction surgery were invited to fill out an additional survey concerning donor sites. The BODY-Q was utilized for data collection. Results of AFT patients were compared to a control group: implant-based reconstruction patients who do not have a donor site. RESULTS: A total of 51 patients (20 control, 31 intervention) completed the questionnaire. No statistical differences in satisfaction with body were found between these groups. The most frequent complaint was contour irregularities (31 reports, 60.8%) with the least favorable donor site being thighs (23 reports, 53.5%) in the AFT group. CONCLUSIONS: There is no difference in satisfaction with body between breast cancer patients receiving AFT or IBR, meaning that large volume liposuction does not aesthetically affect the utilized donor sites. Nevertheless, reconstructive surgeons should be aware of possible donor site complications, especially contour irregularities at the thighs, and discuss this with their patients

Donor site complications and satisfaction in autologous fat grafting for breast reconstruction:A systematic review

BACKGROUND: Breast cancer is the most common cancer in females worldwide. One option for total breast reconstruction following total breast amputation is autologous fat transfer (AFT). However, this is still an upcoming reconstruction technique, and little is known about the donor site complications and their influence on the patient's overall satisfaction. OBJECTIVES: This systematic review aims to review the current literature regarding donor site complications and donor site satisfaction following AFT for total breast reconstruction. SEARCH METHODS: A literature search was performed in PubMed, Web of Science, Embase, Cochrane, TRIP pro, and Prospero. All published original literature reporting on complications or satisfaction at the donor site in patients who underwent liposuction, followed by high-volume lipofilling was considered. MAIN RESULTS: This systematic review resulted in the inclusion of 21 cohort studies, consisting of 2241 participants. None of the studies reported donor site satisfaction scores of any kind. The most frequently reported donor site complication was ecchymosis (268 cases), followed by pain (122 cases), haematoma (58 cases), irregularities (12 cases), burns (four cases), and infection (three cases). Reports on follow-up and management of donor site complications were generally lacking. AUTHOR'S CONCLUSIONS: Results regarding the donor site are inconclusive. Pre-specified complications, a standardized manner of reporting, long-term follow-up, and patient-reported outcome measures are lacking in most of the studies. The impact of the donor site on quality of life after autologous fat grafting in breast reconstruction remains a blind spot. PROSPERO registration number: CRD42020222870

Somatotopic mapping of the human breast using 7 T functional MRI

How are tactile sensations in the breast represented in the female and male brain? Using ultra high-field 7 T MRI in ten females and ten males, we demonstrate that the representation of tactile breast information shows a somatotopic organization, with cortical magnification of the nipple. Furthermore, we show that the core representation of the breast is organized according to the specific nerve architecture that underlies breast sensation, where the medial and lateral sides of one breast are asymmetrically represented in bilateral primary somatosensory cortex. Finally, gradual selectivity signatures allude to a somatotopic organization of the breast area with overlapping, but distinctive, cortical representations of breast segments. Our univariate and multivariate analyses consistently showed similar somatosensory breast representations in males and females. The findings can guide future research on neuroplastic reorganization of the breast area, across reproductive life stages, and after breast surgery