{"id":18687,"date":"2020-03-11T15:46:08","date_gmt":"2020-03-11T14:46:08","guid":{"rendered":"https:\/\/wwwdev.embl.org\/news\/?p=18687"},"modified":"2024-03-22T11:28:32","modified_gmt":"2024-03-22T10:28:32","slug":"research-leukaemia-causes-and-therapies","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/research-leukaemia-causes-and-therapies\/","title":{"rendered":"\u20ac2.45 m to investigate leukaemia causes and therapies"},"content":{"rendered":"\n

Leukaemia stem cells are considered to be the starting point of leukaemia; their elimination is a basic prerequisite for a successful long-term therapy. Scientists at Heidelberg University Hospital (UKHD), the Heidelberg Institute for Stem Cell Technology and Experimental Medicine at the German Cancer Research Center (HI-STEM\/DKFZ), the German Cancer Research Center (DKFZ) and the European Molecular Biology Laboratory (EMBL) have now obtained research funding of \u20ac2.45 million from the German Federal Ministry of Education and Research (BMBF) as part of the junior research alliance LeukoSyStem. The aim of their project is to investigate the cells that are the origin of acute myeloid leukaemia (AML) and thus \u201cget to the root of the problem\u201d. The scientists intend to use isolated single cells from patient samples to investigate characteristic markers, mutations, functional data, and metabolic pathways, to gain a better understanding of leukaemia stem cells and their environment in bone marrow. The collected data will be evaluated comprehensively with the help of computer algorithms specially developed for the purpose.<\/p>\n\n\n\n

Leukemia stem cells as the origin of a disease that is often fatal<\/h3>\n\n\n\n

The development of normal, healthy blood cells starts from haematopoietic stem cells in the bone marrow and proceeds through various stages of so-called precursor cells. In each of these stages, the accumulation of mutations can lead to cell degeneration and the development of blood cancer (leukaemia).<\/p>\n\n\n\n

Acute myeloid leukaemia (AML) is the most common form of leukaemia in adults. In AML, mutated, functionless blood cells \u2013 known as blasts \u2013 overgrow other bone marrow cells. Every year in Europe, three to five out of every 100 000 people receive a diagnosis of AML. Despite therapeutic options such as chemotherapy and stem cell transplantation, relapses are frequent and the five-year survival rate for patients up to the age of 60 is 35\u201340%. For patients above 60, it is only 5\u201310%.<\/p>\n\n\n\n

A basic prerequisite for the effective cure of patients is the targeted elimination of the leukaemia\u2019s starting cells, called leukaemia stem cells. \u201cFor therapy, we need to find the cause of the problem and tackle the leukaemia stem cells,\u201d says Dr. med. Simon Raffel, project partner from the Department of Haematology, Oncology and Rheumatology (Medical Director: Prof. Dr. Carsten M\u00fcller-Tidow) at UKHD. Like healthy stem cells, leukaemia stem cells are located in the stem cell niche in the bone marrow and are able to constantly produce new leukaemia cells (blasts). The interaction of leukaemia stem cells with other factors and cells of the stem cell niche is not yet fully understood. This is where the currently approved junior research alliance comes in, which comprises three sub-projects: the analysis of single leukaemia stem cells, an investigation of the stem cell niche in the bone marrow, and a systems medical, comprehensive evaluation of the collected data.<\/p>\n\n\n\n

In the stem cell niche, healthy and non-functional blood cells thrive equally<\/h3>\n\n\n\n

Dr. Simon Raffel from UKHD, in cooperation with Dr. Lars Velten of the Centre for Genomic Regulation (CRG), in Barcelona, Spain, will investigate the characteristics of leukaemia stem cells of AML patients in comparison with healthy blood cells. For this purpose, patient cells are isolated and surface markers, specific mutations, cell functions, and special metabolic properties of diseased cells are compared to healthy cells.<\/p>\n\n\n\n

The leukaemia stem cells are located in the patient\u2019s bone marrow \u2013 in the stem cell niche \u2013 which contains a diverse range of cells, such as immune, blood vessel, and connective tissue cells. To investigate their contribution to the development of leukaemia and resistance to therapy, the project coordinator and project leader Dr. Simon Haas (HI-STEM\/DKFZ) will develop novel single-cell and spatially resolved analysis methods and use them to systematically investigate the AML microenvironment. \u201cWith our work, we hope to gain a better understanding of the pathogenesis and therapy resistance mechanisms of AML as a whole, which in the medium term will lead to new diagnostic and therapeutic options,\u201d says Simon Haas.<\/p>\n\n\n\n

In the third sub-project, the data collected using different methods will be evaluated by physicist and mathematician Dr. Laleh Haghverdi from EMBL. She will develop new bioinformatics methods and algorithms for integration and analysis in a systems biology approach. \u201cPrevious studies have looked at individual aspects of leukaemia cells, be they DNA mutations, RNA, or metabolic factors. We are now specifically aiming to use a comprehensive approach to investigate the interaction of multiple aspects of AML,\u201d she explains.<\/p>\n\n\n\n

Fighting leukemia cells, sparing healthy cells<\/h3>\n\n\n\n

The researchers are particularly interested in being able to better distinguish between healthy and leukaemia stem cells, as this is only possible to a limited extent using existing markers. Only when this can be done more precisely can new biomarkers for the discovery of the mutated cells be identified, opening up possible new points of attack for targeted therapies. \u201cThe treatment of AML will be all the more successful the more precisely we can specifically eliminate the leukaemia\u2019s starting cells and spare the healthy blood cells in the future,\u201d says Simon Raffel.<\/p>\n\n\n\n

The funding of the junior research alliance LeukoSyStem by the German Federal Ministry of Education and Research (BMBF) enables the young scientists from Heidelberg to carry out interdisciplinary research in systems medicine. The project started at the beginning of 2020. The total funding amounts to approximately \u20ac2.45 million over five years, with a share of approximately \u20ac1.3 million for the Department of Haematology, Oncology and Rheumatology at UKHD.<\/p>\n\n\n\n

The development of normal, healthy blood cells starts from haematopoietic stem cells in the bone marrow and proceeds through various stages of so-called precursor cells. In each of these stages, the accumulation of mutations can lead to cell degeneration and the development of blood cancer (leukaemia). <\/p>\n\n\n\n\n

Related links<\/h3>\n

Department of Haematology, Oncology and Rheumatology at Heidelberg University Hospital<\/a>
HI-STEM: The Heidelberg Institute for Stem Cell Technology and Experimental Medicine<\/a>
LeukoSyStem<\/a><\/p>\n<\/div>\n\n\n

\n\n\n\n

2,45 Millionen Euro zur Erforschung von Ursachen und Therapie bei Leuk\u00e4mie<\/h2>\n\n\n\n

Der Heidelberger LeukoSyStem-Verbund erforscht Leuk\u00e4miestammzellen bei akuter myeloischer Leuk\u00e4mie (AML). Das Bundesministeriums f\u00fcr Bildung und Forschung unterst\u00fctzt diese Kooperation desUniversit\u00e4tsklinikums Heidelberg, HI-STEM (Deutsches Krebsforschungszentrum) und des Europ\u00e4ischen Laboratoriums f\u00fcr Molekularbiologie. Dies ist eine gemeinsame Pressemitteilung des Universit\u00e4tsklinikums Heidelberg, des Deutschen Krebsforschungszentrums und des Europ\u00e4ischen Laboratoriums f\u00fcr Molekularbiologie.<\/p>\n\n\n\n

\"\"
Die Leuk\u00e4miestammzellen befinden sich im Knochenmark des Patienten (hier blau eingef\u00e4rbt) in der so genannten Stammzellnische. Die gr\u00fcne Struktur zeigt den Knochen selbst. Bildquelle: Dr. Raphael Lutz, Haas Lab<\/figcaption><\/figure>\n\n\n\n

Leuk\u00e4miestammzellen gelten als Ausgangspunkt einer Leuk\u00e4mie; ihre Eliminierung ist Grundvoraussetzung f\u00fcr eine langfristig erfolgreiche Therapie. Wissenschaftlerinnen und Wissenschaftler des Universit\u00e4tsklinikums Heidelberg (UKHD), des Heidelberger Instituts f\u00fcr Stammzelltechnologie und Experimentelle Medizin im Deutschen Krebsforschungszentrum (HI-STEM\/DKFZ) und des Europ\u00e4ischen Laboratoriums f\u00fcr Molekularbiologie (EMBL) konnten nun im Rahmen des Junior-Verbundes LeukoSyStem eine Forschungsf\u00f6rderung des Bundesministeriums f\u00fcr Bildung und Forschung (BMBF) in H\u00f6he von 2,45 Millionen Euro einwerben. Ziel ihres Projektes ist es, die Ursprungszellen der akuten myeloischen Leuk\u00e4mie (AML) zu erforschen und auf diese Weise das \u00dcbel sozusagen \u201ebei der Wurzel\u201c zu packen. Die Wissenschaftler wollen anhand von isolierten Einzelzellen aus Patientenproben charakteristische Marker, Mutationen, Funktionsdaten und Stoffwechselwege untersuchen, um Leuk\u00e4miestammzellen und ihre Umgebung im Knochenmark besser verstehen zu k\u00f6nnen. Die gesammelten Daten sollen mithilfe neu zu entwickelnder Computer-Algorithmen \u00fcbergreifend ausgewertet werden.<\/p>\n\n\n\n

Leuk\u00e4mische Stammzellen als Ursache einer h\u00e4ufig t\u00f6dlich verlaufenden Krankheit<\/h3>\n\n\n\n

Die Entwicklung normaler, gesunder Blutzellen geht von h\u00e4matopoetischen Stammzellen im Knochenmark aus und verl\u00e4uft \u00fcber verschiedene Stadien sogenannter Vorl\u00e4uferzellen. Dabei kann es in jedem dieser Stadien durch Anh\u00e4ufung von Mutationen zur Entartung von Zellen und der Entwicklung von Blutkrebs (Leuk\u00e4mie) kommen.<\/p>\n\n\n\n

Die akute myeloische Leuk\u00e4mie (AML) ist die h\u00e4ufigste Form der Leuk\u00e4mie im Erwachsenenalter, bei der mutierte, funktionslose Blutzellen, sogenannte Blasten, die anderen Knochenmarkszellen \u00fcberwuchern. In Europa erkranken j\u00e4hrlich drei bis f\u00fcnf Patienten je 100.000 Einwohner an AML. Trotz Therapiem\u00f6glichkeiten wie Chemotherapie und Stammzelltransplantation kommt es h\u00e4ufig zu R\u00fcckf\u00e4llen und die F\u00fcnf-Jahres-\u00dcberlebenswahrscheinlichkeit f\u00fcr Patienten unter 60 Jahren liegt bei 35 bis 40 Prozent und f\u00fcr Patienten \u00fcber 60 Jahren bei nur f\u00fcnf bis zehn Prozent.<\/p>\n\n\n\n

Als Grundvoraussetzung f\u00fcr eine effektive Heilung der Patienten gilt die gezielte Eliminierung der Ausgangszellen der Leuk\u00e4mie, den sogenannten Leuk\u00e4miestammzellen. \u201eZur Therapie m\u00fcssen wir die Ursache des Problems finden und die leuk\u00e4mischen Stammzellen angehen\u201c, sagt Dr. med. Simon Raffel, Projektpartner von der Medizinischen Klinik f\u00fcr H\u00e4matologie, Onkologie, Rheumatologie (\u00c4rztlicher Direktor: Prof. Dr. Carsten M\u00fcller-Tidow) des Universit\u00e4tsklinikums Heidelberg. Die Leuk\u00e4miestammzellen befinden sich wie die gesunden Stammzellen auch in der Stammzellnische im Knochenmark und sind in der Lage, st\u00e4ndig neue Leuk\u00e4miezellen (Blasten) zu bilden. Das Zusammenspiel von Leuk\u00e4miestammzellen mit anderen Faktoren und Zellen der Stammzellnische ist noch nicht ausreichend gekl\u00e4rt. Hier setzt das aktuell bewilligte Juniorverbund-Projekt an, das drei Teilprojekte umfasst: die Einzelzellanalyse leuk\u00e4mischer Stammzellen, eine Untersuchung der Stammzellnische im Knochenmark und eine systemmedizinische, \u00fcbergreifende Auswertung der gesammelten Daten.<\/p>\n\n\n\n

In der Stammzellnische gedeihen gesunde und funktionslose Blutzellen gleicherma\u00dfen<\/h3>\n\n\n\n

Dr. Simon Raffel vom Universit\u00e4tsklinikum Heidelberg wird in Kooperation mit Dr. Lars Velten (Centre for Genomic Regulation, Barcelona, Spanien) Charakteristika von Leuk\u00e4miestammzellen von AML-Patienten im Vergleich zu gesunden Blutzellen untersuchen. Hierzu werden Patientenzellen isoliert, vereinzelt und Oberfl\u00e4chenmarker, spezifische Mutationen, Zellfunktionen sowie spezielle Stoffwechseleigenschaften der kranken im Vergleich zu den gesunden Zellen betrachtet. <\/p>\n\n\n\n

Die Leuk\u00e4miestammzellen befinden sich im Knochenmark des Patienten in der so genannten Stammzellnische, deren Milieu durch weitere Zellen wie Immun-, Blutgef\u00e4\u00df- und Bindegewebszellen gepr\u00e4gt ist. Um deren Beitrag an der Entstehung und Therapieresistenz von Leuk\u00e4mien genauer zu erforschen, wird der Projektkoordinator und Teilprojektleiter Dr. Simon Haas (HI-STEM\/DKFZ) neuartige Einzelzell- und r\u00e4umlich-aufgel\u00f6ste Analysemethoden entwickeln und mit Hilfe dieser das AML Mikromilieu systemisch untersuchen. \u201eMit unseren Arbeiten m\u00f6chten wir die Pathogenese und Therapieresistenzmechanismen der AML in ihrer Gesamtheit besser verstehen lernen, was mittelfristig zu neuartigen Diagnose- und Therapieoptionen f\u00fchren soll\u201c, fasst Simon Haas zusammen.<\/p>\n\n\n\n

Die mit verschiedenen Methoden gesammelten Daten werden im dritten Teilprojekt von der Physikerin und Mathematikerin Dr. Laleh Haghverdi vom EMBL ausgewertet. Hierf\u00fcr wird sie neue bioinformatische Methoden und Algorithmen zur Integration und Analyse im Sinne eines systembiologischen Ansatzes entwickeln. \u201eIn bisherigen Untersuchungen wurden einzelne Aspekte der Leuk\u00e4miezellen betrachtet, seien es DNA-Mutationen, RNA oder metabolische Faktoren. Wir zielen nun speziell darauf ab, mit einem \u00fcbergreifenden Ansatz das Zusammenwirken multipler Aspekte der AML zu untersuchen\u201c, erkl\u00e4rt Laleh Haghverdi.<\/p>\n\n\n\n

Ausgangszellen der Leuk\u00e4mie bek\u00e4mpfen, gesunde Zellen schonen<\/h3>\n\n\n\n

Besonders eine bessere Unterscheidung von gesunden und leuk\u00e4mischen Stammzellen ist den Forschern wichtig, da diese anhand bisheriger Marker nur begrenzt m\u00f6glich ist. Nur mit einer genaueren Differenzierung lassen sich neue Biomarker zur Entdeckung der mutierten Zellen und damit Angriffspunkte f\u00fcr eine gezielte Therapie herausfinden. \u201eDie Behandlung der AML wird umso erfolgreicher, je genauer wir in Zukunft spezifisch die Ausgangszellen der Leuk\u00e4mie eliminieren und die gesunden Blutzellen verschonen k\u00f6nnen\u201c, so Simon Raffel.<\/p>\n\n\n\n

Mit der F\u00f6rderung des Juniorverbunds LeukoSyStem durch das Bundesministerium f\u00fcr Bildung und Forschung (BMBF) erhalten die Heidelberger Nachwuchswissenschaftler die M\u00f6glichkeit, Forschungsarbeiten zur Systemmedizin interdisziplin\u00e4r zu realisieren. Das Projekt startet Anfang 2020, die Gesamtf\u00f6rdersumme betr\u00e4gt ca. 2,45 Mio. Euro f\u00fcr f\u00fcnf Jahre, mit einem Anteil von rund. 1,3 Mio. f\u00fcr die Medizinische Klinik f\u00fcr H\u00e4matologie, Onkologie, Rheumatologie des UKHD.<\/p>\n\n\n\n\n

Weiterf\u00fchrende Links<\/h3>\n

Abteilung f\u00fcr H\u00e4matologie, Onkologie und Rheumatologie der Universit\u00e4tsklinik Heidelberg<\/a>
HI-STEM: Heidelberger Institut f\u00fcr Stammzelltechnologie und Experimentelle Medizin<\/a>
LeukoSyStem<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

The Heidelberg-based LeukoSyStem consortium investigates leukaemia stem cells in acute myeloid leukaemia. The German Federal Ministry of Education and Research financially supports this collaboration between Heidelberg University Hospital, HI-STEM gGmbH, the German Cancer Research Center and EMBL.<\/p>\n","protected":false},"author":71,"featured_media":18700,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17597,2],"tags":[1307,1306,1748],"embl_taxonomy":[],"class_list":["post-18687","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-embl-announcements","category-science","tag-dkfz","tag-leukaemia","tag-press-release"],"acf":{"featured":true,"article_intro":"

The Heidelberg-based LeukoSyStem consortium investigates leukaemia stem cells in acute myeloid leukaemia. The German Federal Ministry of Education and Research financially supports this collaboration between Heidelberg University Hospital, HI-STEM gGmbH, the German Cancer Research Center and EMBL.<\/p>\n","article_sources":false,"related_links":false,"color":"#193f90","pdf_archive_link":"","description_pdf_archive_link":"","vf_locked":false,"show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":[{"translation_language":"German","translation_anchor":"#de"}],"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"\n\u20ac2.45 m to investigate leukaemia causes and therapies | EMBL<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/research-leukaemia-causes-and-therapies\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\u20ac2.45 m to investigate leukaemia causes and therapies | EMBL\" \/>\n<meta property=\"og:description\" content=\"The Heidelberg-based LeukoSyStem consortium investigates leukaemia stem cells in acute myeloid leukaemia. 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