Aggressiveness of Acute Myeloid Leukemia Elucidated

Acute Myeloid Leukaemia Awareness RibbonScientists at the Friedrich Miescher Institute for Biomedical Research (FMI) and the University of Basel have discovered why acute leukaemia with the same genetic abnormality vary in their aggressiveness based on their cellular origin. They found that the cancer inducing alteration is particularly devastating if it occurs in early hematopoietic stem cells expressing certain genes involved in cell migration and tissue invasion.

These findings should now make it possible to classify patients into more clearly defined groups, to adapt treatment, and hopefully also to develop personalized therapeutic strategies for the future.

Acute Myeloid Leukemia (AML) is a blood cancer caused by various genetic abnormalities in hematopoietic precursor cells which lead to the proliferation of immature white blood cells. As a result, the bone marrow is no longer able to produce normal blood cells. AML can be treated with chemotherapy; however, even in cases with the same genetic abnormality, disease progression often varies. It has not been clear to date why certain forms are more aggressive than others.

Research teams led by Antoine Peters, a Group Leader at the FMI, and by Jürg Schwaller of the University of Basel, Department of Biomedicine and the University Children’s Hospital Basel (UKBB) have now discovered that the aggressiveness of a certain form of AML largely depends on the type of precursor cell in which the genetic alteration occurs. Schwaller says: “These so-called MLL fusion leukaemia affect not only very young patients but also patients over 60 who have already undergone chemotherapy.”

Using a mouse model, the researchers showed that the prognosis for this disease is particularly poor if the genetic alteration occurs in hematopoietic stem cells. This type of AML is highly aggressive and is associated with extensive tissue infiltration and resistance to chemotherapy.

The researchers also found that these hematopoietic stem cells express certain genes which promote cell migration and tissue invasion. In later-stage precursor cells, these genes were no longer expressed. Peters notes: “When we reduced expression of one of these genes in the early hematopoietic stem cells, disease progression was much milder.

Importantly, the findings in mice are also applicable to humans: in samples collected from patients with an aggressive disease course, exactly the same genes were expressed. Peters concludes: “The prognosis thus depends on the particular hematopoietic stem or precursor cells in which the genetic alteration occurs, and what genes are expressed.

As Schwaller explains, these genes could also serve as biomarkers: “The expression of genes such as EVI1, ERG or ZEB1 now allows us to classify patients into different groups according to prognosis, and if necessary to adapt treatment. Our findings should also enable us to develop new, more personalized therapies for these patients.

This project was supported by the Swiss National Science Foundation and by the Cell Plasticity program.



Medical News Today

Article: MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome, Vaia Stavropoulou, Susanne Kaspar, Laurent Brault, Mathijs A. Sanders, Sabine Juge, Stefano Morettini, Alexandar Tzankov, Michelina Iacovino, I-Jun Lau, Thomas A. Milne, Hélène Royo, Michael Kyba, Peter J.M. Valk, Antoine H.F.M. Peters, Juerg Schwaller, Cancer Cell, doi: 10.1016/j.ccell.2016.05.011, published online 23 June 2016.




About LFCT

This is a blog about CHILDHOOD CANCER and CHILDHOOD CANCER AWARENESS Little Fighters Cancer Trust is a non-profit organisation that offers support and aid to Children with Cancer and their families. When a child is diagnosed with cancer it affects the whole family. One of the parents, usually the mother, must give up their job to care for the child and this creates financial problems for the family. In South Africa especially the majority of these families are not well-to-do; many of them are rural. A diagnosis of cancer can wipe out any family’s finances, let alone a poor family. The costs of special medications, special diets, hospital stays, transport to and from the hospital or clinic and accommodation and food costs for the mother who spends most of the time at her child’s bedside are astronomical. These are the people and problems that fall through the cracks, and these are the people that Little Fighters Cancer Trust has pledged to help in any way possible. LFCT takes a holistic approach to assisting the Children with Cancer and their Families, with the main aim to be the preservation of individual dignity and pride. Little Fighters Cancer Trust also focuses on promotion and advocacy of National Childhood Cancer Awareness in an effort to increase awareness of Early Warning Signs of Childhood Cancer. This would result in earlier diagnosis, giving the Child with Cancer more of a chance at Treatment and Survival. See "About" for more Background info

Posted on 14 July, 2016, in Blog, Research. Bookmark the permalink. Leave a comment.

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