TEARDRoP Oncology: BBRMI.be workshop on sustainability

With the support of the Olivia Hendrickx Research Fund, the ‘Team EARly DRug development in Paediatric oncology (TEARDRoP)’ consortium was founded. As the name indicates, this consortium was set up to support the translation of new research findings in the field of paediatric oncology to new therapeutic options, making science find its way to children in need of new and better treatments. In specific, the consortium will help bridge the gap between basic and clinical research through stimulating close collaborations and supporting biobanking efforts. Therefor I write and bring in to (clinical) practice practical flows for the biobanking of human body material for (inter)national academic clinical studies and general research, as well as support the set-up of a national pediatric-specific biobank collection. The access to patient material via this biobanking effort is crucial for the translation of (basic) research findings to the clinic, and is of utmost importance for the development and selection of the best fit treatment for each patient, the focus of personalized medicine. Thanks to the support of the Olivia Fund, I was appointed as coordinator of this consortium, under the direct supervision of paediatric oncologist Prof. Dr. Bram De Wilde (UZ Gent, CRIG), Prof. Dr. Catherine Van Der Straeten (HIRUZ UZ Gent), and Prof. Dr. Tim Lammens (UGent, CRIG). To ensure all (Belgian) patients benefit from the initiative, the TEARDRoP consortium has a close partnership with the ‘Belgian Society of Pediatric Haematology Oncology (BSPHO)’, an organization that has been supporting academic research into children’s cancer for years

The TEARDRoP (Team early drug development in Paediatric oncology) consortium : to help Research find its way to improved treatments for children with cancer

Liselot Mus THE TEARDRoP (Team EARly DRug development in Paediatric oncology) CONSORTIUM: TO HELP RESEARCH FIND ITS WAY TO IMPROVED TREATMENTS FOR CHILDREN WITH CANCER With the support of the Olivia Hendrickx Research Fund, the ‘Team EARly DRug development in Paediatric oncology (TEARDRoP)’ consortium was founded. As the name indicates, this consortium was set up to support the translation of new research findings in the field of paediatric oncology to new therapeutic options, making science find its way to children in need of new and better treatments. In specific, the consortium will help bridge the gap between basic and clinical research through stimulating close collaborations and supporting biobanking efforts. The access to patient material via this biobanking effort is crucial for the translation of (basic) research findings to the clinic, and is of utmost importance for the development and selection of the best fit treatment for each patient, the focus of personalized medicine. Thanks to the support of the Olivia Fund, former CRIG researcher Dr. Ir. Liselot Mus could be appointed as coordinator of this consortium, under the direct supervision of paediatric oncologist Prof. Dr. Bram De Wilde (UZ Gent, CRIG) and of Prof. Dr. Catherine Van Der Straeten, head of the ‘Health, innovation and research institute (HIRUZ)’ of UZ Gent. To ensure all (Belgian) patients benefit from the initiative, the TEARDRoP consortium has a close partnership with the ‘Belgian Society of Pediatric Haematology Oncology (BSPHO)’, an organization that has been supporting academic research into children’s cancer for years. On the 28th of June 2021, the consortium was officially launched by Mrs. Ilse De Reze (chair of the Olivia Fund), Prof. Dr. Bram De Wilde and Dr. Ir. Liselot Mus. As several CRIG teams work on paediatric oncology and are therefore directly involved in the ‘TEARDRoP’ consortium, this initiative is also a strong boost for our CRIG research

TEARDRoP Oncology: Good practices for paediatric biobanking

With the support of the Olivia Hendrickx Research Fund, the ‘Team EARly DRug development in Paediatric oncology (TEARDRoP)’ consortium was founded to support the translation of new research findings in the field of pediatric oncology to new therapeutic options, making science find its way to children in need of new and better treatments. In specific, the consortium aims to support biobanking efforts through a bottom-up approach by: (i) bringing in to (clinical) practice practical flows for the biobanking of human body material for (inter)national academic clinical studies and general research, embedded into routine in order to help healthcare workers, (ii) set-up a national pediatric oncological-specific biobank collection as these are rare and precious materials The longitudinal collection and access to patient material via this biobanking effort is crucial for the translation of (basic) research findings to the clinic, and is of utmost importance for the development and selection of the best fit treatment for each patient, the focus of personalized medicine. To ensure all (Belgian) patients benefit from the initiative, the TEARDRoP consortium has a close partnership with the ‘Belgian Society of Pediatric Haematology Oncology (BSPHO)’, an organization that has been supporting academic research into children’s cancer for years

Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis?

Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis

Deciphering molecular heterogeneity in pediatric AML using a cancer vs. normal transcriptomic approach

Background Still 30–40% of pediatric acute myeloid leukemia (pedAML) patients relapse. Delineation of the transcriptomic profile of leukemic subpopulations could aid in a better understanding of molecular biology and provide novel biomarkers. Methods Using microarray profiling and quantitative PCR validation, transcript expression was measured in leukemic stem cells (LSC, n = 24) and leukemic blasts (L-blast, n = 25) from pedAML patients in comparison to hematopoietic stem cells (HSCs, n = 19) and control myeloblasts (C-blast, n = 20) sorted from healthy subjects. Gene set enrichment analysis was performed to identify relevant gene set enrichment signatures, and functional protein associations were identified by STRING analysis. Results Highly significantly overexpressed genes in LSC and L-blast were identified with a vast majority not studied in AML. CDKN1A, CFP, and CFD (LSC) and HOMER3, CTSA, and GADD45B (L-blast) represent potentially interesting biomarkers and therapeutic targets. Eleven LSC downregulated targets were identified that potentially qualify as tumor suppressor genes, with MYCT1, PBX1, and PTPRD of highest interest. Inflammatory and immune dysregulation appeared to be perturbed biological networks in LSC, whereas dysregulated metabolic profiles were observed in L-blast. Conclusion Our study illustrates the power of taking into account cell population heterogeneity and reveals novel targets eligible for functional evaluation and therapy in pedAML. Impact Novel transcriptional targets were discovered showing a significant differential expression in LSCs and blasts from pedAML patients compared to their normal counterparts from healthy controls. Deregulated pathways, including immune and metabolic dysregulation, were addressed for the first time in children, offering a deeper understanding of the molecular pathogenesis. These novel targets have the potential of acting as biomarkers for risk stratification, follow-up, and targeted therapy. Multiple LSC-downregulated targets endow tumor suppressor roles in other cancer entities, and further investigation whether hypomethylating therapy could result into LSC eradication in pedAML is warranted

DECIPHERING THE NON-CODING RNA LANDSCAPE OF PEDIATRIC ACUTE MYELOID LEUKEMIA

DECIPHERING THE NON-CODING RNA LANDSCAPE OF PEDIATRIC ACUTE MYELOID LEUKEMI

Sociodemographic and medical determinants of quality of life in long-term childhood acute lymphoblastic leukemia survivors enrolled in EORTC CLG studies

Simple Summary Long-term quality of life and its potential risk factors in childhood acute lymphoblastic leukemia (ALL) patients remain uncertain. In this cross-sectional study, we investigated daily life quality and life challenges in adult survivors of ALL using multiple self-report questionnaires. Furthermore, risk factors, including gender, age at diagnosis, relapse/second neoplasm, risk group, and cranial radiotherapy, were explored in detail. Younger, female, and relapsed patients appeared to encounter more life challenges, while physical challenges occurred more often in relapsed and high-risk patients. More positive effects on socializing were found in the older patients compared to younger patients. This study provides important information for individual and specialized support. Background: due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive. We investigated potential risk factors for decreased daily life quality and life challenges in long-term childhood ALL survivors enrolled between 1971 and 1998 in EORTC studies. Methods: self-report questionnaires were collected from 186 survivors (109 females; mean age at diagnosis 5.62 years, range 0.2-14.7; median time since diagnosis of 20.5 years (12.9-41.6)), including the Short-Form Health Survey (SF-12) and Impact of Cancer-Childhood Survivors (IOC-CS). Multivariable linear regression models were used to assess the impact of gender, age at diagnosis, relapse/second neoplasm, National Cancer Institute (NCI) risk group and cranial radiotherapy on 2 subscales of the SF-12 (physical and mental health) and five subscales of the IOC-CS (life challenges, body and health, personal growth, thinking and memory problems and socializing). Results: mental component scores of SF-12 were not significantly associated with any risk factor. Physical component scores were lower in relapsed, irradiated and NCI high-risk patients. Regarding IOC-CS negative impact subscales, life challenges was more negatively impacted by cancer in female, younger (i.e., 6 years). Conclusions: this study demonstrates that long-term outcomes can be both adverse and positive, depending on the patient's demographic and clinical characteristics. Younger, female, and relapsed patients might encounter more life challenges years after their disease, while physical challenges could occur more often in relapsed and high-risk patients. Finally, the positive effect on socializing in the older patients sheds new light on the importance of peer interactions for this subgroup. Specific individual challenges thus need specialized support for specific subgroups

Sociodemographic and medical determinants of quality of life in long-term childhood acute lymphoblastic leukemia survivors enrolled in EORTC CLG studies

Background: due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive. We investigated potential risk factors for decreased daily life quality and life challenges in long-term childhood ALL survivors enrolled between 1971 and 1998 in EORTC studies. Methods: self-report questionnaires were collected from 186 survivors (109 females; mean age at diagnosis 5.62 years, range 0.2–14.7; median time since diagnosis of 20.5 years (12.9–41.6)), including the Short-Form Health Survey (SF-12) and Impact of Cancer-Childhood Survivors (IOC-CS). Multivariable linear regression models were used to assess the impact of gender, age at diagnosis, relapse/second neoplasm, National Cancer Institute (NCI) risk group and cranial radiotherapy on 2 subscales of the SF-12 (physical and mental health) and five subscales of the IOC-CS (life challenges, body and health, personal growth, thinking and memory problems and socializing). Results: mental component scores of SF-12 were not significantly associated with any risk factor. Physical component scores were lower in relapsed, irradiated and NCI high-risk patients. Regarding IOC-CS negative impact subscales, life challenges was more negatively impacted by cancer in female, younger (i.e., &lt;6 years) and relapsed patients. Regarding the positive impact scales, personal growth was more positively impacted in relapsed patients, whereas body and health, and socializing, were less positively impacted in these patients, compared to non-relapsed patients. Socializing was more positively impacted in older patients (&gt;6 years). Conclusions: this study demonstrates that long-term outcomes can be both adverse and positive, depending on the patient’s demographic and clinical characteristics. Younger, female, and relapsed patients might encounter more life challenges years after their disease, while physical challenges could occur more often in relapsed and high-risk patients. Finally, the positive effect on socializing in the older patients sheds new light on the importance of peer interactions for this subgroup. Specific individual challenges thus need specialized support for specific subgroups.</p