Young Investigators in EuNet-INNOCHRON are all researchers less than forty years old and Early Career Investigators (ECI) those who are within a time span of up to 8 years from the date they obtained their PhD/doctorate. EuNet-INNOCHRON wishes to promote training and education of the younger researchers and to give opportunities to ECIs to expand their ideas through a number of collaborative activities including exchanges between participating Institutions. The Action aims to maximally use the Networking Tools that COST offers such as Conference grants, Training Schools and Short Term Scientific Missions. We enthusiastically promote the idea to generate within EuNet-INNOCHRON the Next Generation of researchers and physician scientists with expertise in Neutropenia. Welcome Aboard!
Your ideas are welcome!
Severe congenital neutropenia (CN) is a pre-leukemia bone marrow failure syndrome presented with profound neutropenia early after birth due to markedly diminished granulocytic differentiation of bone marrow hematopoietic stem and progenitor cells (HSPCs). G-CSF is the first-choice therapy in CN patients (Bonilla et al. 1989; Dale et al. 1993).
With the advent of next generation sequencing, the discovery of causative genetic variants of human inherited diseases has rapidly accelerated. As a result, germline mutations in more than 25 genes were identified to be associated with CN (Skokowa et al. 2017). Based on the data from the Severe Congenital Neutropenia International Registry (SCNIR) database, mutations in ELANE is responsible for the majority of CN cases (n=139, 26,6%) (Figure 1), whereas the second biggest group (n=123, 23,5%) after ELANE-CN cohort comprises unclassified cases, where a genetic diagnosis could not be established so far.
Figure 1. Distribution of CN patients in the SCNIR database according to their genetic diagnosis (status on 10/2019).
Precise genetic diagnosis in patients with genetically unclassified severe congenital neutropenia enables improved therapeutic surveillance and better patient management by clinicians.
Aims:
The results of exome sequencing/trio analysis will be ready in 3 months. In the case of identification of novel candidate mutations/genes the collaboration can be extended to generation of patient iPSCs followed by CRISPR/Cas9 correction of candidate variant and/or variant pathogenicity evaluation in a zebrafish model.
Participation in the initiative is open for all members of the Young EuNET-INNOCHRON
For the enrollment of patients in the study and before sample submission please contact Maksim Klimiankou, PhD Maksim.Klimiankou@med.uni-tuebingen.de.
For question regarding the clinical diagnosis of neutropenia please contact Prof. Dr. Julia Skokowa, Julia.Skokowa@med.uni-tuebingen.de
Inclusion and exclusion criteria for patients in the study
Important!
Signed “Informed consent form for adult patients or minor patients' parents (legal Guardian)” is required (the form can be found at https://severe-chronic-neutropenia.org/en/forms).
It is recommended that patient(-s) are registered in the Severe Chronic Neutropenia International Registry using “Registration Form” (the form can be found at https://severe-chronic-neutropenia.org/en/forms).
Sample requirements:
We accept:
Samples should be sent to
Maksim Klimiankou, PhD
Division of Translational Oncology
Department of Oncology, Hematology, Clinical Immunology and Rheumatology
University Hospital Tübingen
Otfried-Müller Str. 10
72076 Tübingen
tel: +49-7071/2980258
Figure 2. Project workflow.
Introduction
Severe congenital neutropenia (CN) is a pre-leukemia bone marrow failure syndrome presented with profound neutropenia early after birth due to markedly diminished granulocytic differentiation of bone marrow hematopoietic stem and progenitor cells (HSPCs). Patient with severe congenital neutropenia has high risk of leukemia transformation which was estimated to be 22% after 10 years. The risk of leukemia is even more increased in the CN patients with poor G-CSF response. (Skokowa et al. 2017). The identification of acquired nonsense CSF3R mutations is usually the first evidence of leukemogenic transformation. Screening for CSF3R, RUNX1 and other AML/MDS associated mutations (ASXL1, SUZ12, EP300, NPM1) can be helpful for early detection of malignant transformation (Skokowa et al. 2014).
Project aims:
Participation in the initiative is open and free for all members of the EuNET-INNOCHRON
For the enrollment of patients in the study please contact Maksim Klimiankou, PhD Maksim.Klimiankou@med.uni-tuebingen.de.
For question regarding the clinical diagnosis AML/MDS or neutropenia please contact Prof. Dr. Julia Skokowa, Julia.Skokowa@med.uni-tuebingen.de
Inclusion and exclusion criteria for patients in the study
Important!
Signed “Informed consent form for adult patients or minor patients' parents (legal Guardian)” is required (the form can be found at https://severe-chronic-neutropenia.org/en/forms).
It is recommended that patient(-s) are registered in the Severe Chronic Neutropenia International Registry using “Registration Form” (the form can be found at https://severe-chronic-neutropenia.org/en/forms).
Sample requirements:
We accept:
Samples should be sent to
Maksim Klimiankou, PhD
Division of Translational Oncology
Department of Oncology, Hematology, Clinical Immunology and Rheumatology
University Hospital Tübingen
Otfried-Müller Str. 10
72076 Tübingen
tel: +49-7071/2980258
Project workflow
DNA of CN patients will be subjected to panel sequencing using unique molecular identifiers (UMIs). Integration of UMIs in sequencing reads enables strand specific molecular indexing and thus sequencing error correction which allows to catch up to 0.25% variant allele frequency of acquired mutations. Capture probes of the panel cover entire coding sequence of ASXL1, BCOR, BCORL1, CBL, CEBPA, DNMT3A, EP300, EZH2, FLT3, IDH1, IDH2, JAK2, KDM6A, KRAS, NPM1, NRAS, PHF6, PTPN11, RAD21, RUNX1, SETBP1, SF1, SF3B1, SRSF2, STAG2, SUZ12, TET2, TP53, U2AF1, ZRSR2, CSF3R and “hot-spot” positions in the other 209 genes mutated in AML, MDS and ALL. Sequencing will be performed with target raw reads depth 40000x in PE150 mode. The results will be provided as a panel sequencing report with estimation of clinical significance of identified mutations (Figure 1).
Figure1. Project workflow.
The Young EuNet-INNOCHRON Committee is proud to announce the Online Discussion Club initiative.
Online Discussion Club will be a unique opportunity for young EuNet-INNOCHRON members to present their future or running projects with short online communications open to all EuNet-INNOCHRON members (both young and senior). This should allow young members to exchange views on their projects with other members, possibly finding new collaborations. During the Online Discussion Club initiative, a schedule of incoming funding opportunities for young investigators will be presented as well, to possibly gather research teams interested in. Announcement and registration forms will be available on the EuNet-INNOCHRON web page.
Specific aims of Online Discussion Club:
Each presentation is allowed at most 20 minutes, plus 10 minutes for constructive discussion. Experts in the field of the presented subjects will be eventually invited (EuNet-INNOCHRON committee may invite external experts). An additional Q&A session (10-15 minutes) will be considered.
A further “Workshop on how to write grant proposal - tips and tricks” will be planned within the Online Discussion Club evets.
Online Discussion Club will be conducted through ZOOM platform once a month, and links to each event will be sent by email to all EuNet-INNOCHRON members.
Young EuNet-INNOCHRON members who wish to present their projects/proposals should contact the Young EuNet-INNOCHRON Committee by sending an email to the following addresses: valentino.bezzerri@ospedaliriuniti.marche.it and skakic.anita@gmail.com.
A specific mailing list will be created in order to update all members on the progress of work.
Severe congenital neutropenia (CN) is a pre-leukemia bone marrow failure syndrome presented with profound neutropenia early after birth
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Severe congenital neutropenia (CN) is a pre-leukemia bone marrow failure syndrome presented with profound neutropenia early after birth
More..
Online Discussion Club will be a unique opportunity for young EuNet-INNOCHRON members to present their future or running projects with short online communications. More..