2018 November 28

New roles discovered for hemapoietic stem and progenitor cells in acute myeloid leukaemia

The Stem Cells, Mesenchymal Cancer and Development Group led by Pablo Menéndez at the Josep Carreras Leukaemia Research Institute provide new insights into the nature of the stroma cells that support stem cells in the bone marrow.

Acute myeloid leukemia (AML) is a group of various disorders characterised by the rapid expansion of immature white blood cells in the bone marrow, although the differences between the disorders that collectively make up AML are not known.  The larger population of immature cells does not have the usual infection fighting abilities of normal mature white blood cells and having too many can also lead to a decrease in the number of red blood cells that carry oxygen and platelets that help clotting.

Many patients do not respond well to standard treatments and in these cases not all the leukemia cells are removed so they then relapse.  The cells that give rise to healthy blood cells, but can also start producing leukemia cells (hematopoietic stem and progenitor cells or HSPCs) exist within a matrix of cells known as the stroma in the bone marrow.   The nature of the stoma is not well understood, although it is known that these cells (bone marrow mesenchymal stem cells or BMSCs) play a part in the production of healthy blood cells and also the leukemic process.  By both being in contact and through chemical signalling the BMSCs communicate with the HSPCs and play a part in blood cell production, they are also known to have anti- inflammatory properties and it is believed that they could be used as “live” medicines.   It was to find out more about the BMSCs in the stroma that the Stem Cells, Mesenchymal Cancer and Development Group led by Pablo Menéndez at the Josep Carreras Leukaemia Research Institute carried out this work, led by RafaelDíaz de la Guardia and published in Hematologica in September.

In previous studies the group had found a correlation between the behaviour of BMSC cells from AML patients in the laboratory and the overall survival of these patients.  AML patients are separated in to different risk groups by studying the appearance and certain molecular characteristics of the genetic material in the leukemic cells, from this information doctors can make predictions about patient survival. In this work cells from patients from different risk groups were used, although the different risk groups gave similar results.  The BMSC cells from AML patients all maintained similar properties to cells from healthy individuals in that in the laboratory they supported the survival, multiplication and differentiation of specialised immune cells.  Also blood stem cells (HSPCs) that had been previously exposed to BMSC stroma cells were better at repopulating bones in mice that had lost the ability to make blood cells than those that had been exposed to stroma cells from healthy donors.  Finally, the stroma cells from AML patients had a greater capacity to reduce inflammation in mice with severe colitis than cells from healthy donors.

We are still finding out about the properties of the stroma cells in bone marrow”, Menéndez tells us, “We now know that stroma cells from patients with acute myeloid leukemia retain the ability to encourage healthy blood cell production and also have powerful anti-inflammatory properties.  The challenge is to find out exactly how they contribute to leukemia pathogenesis and how we could possibly harness their powers to fight or reverse the disease.”

Original article

Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis

Rafael Díaz de la Guardia, Belen Lopez-Millan, Heleia Roca-Ho, Clara Bueno, Francisco Gutiérrez-Agüera, Jose Luis Fuster, Eduardo Anguita, Samanta Zanetti, Susana Vives, Josep Nomdedeu, Robert Sackstein, Jessie Lavoie, Elena Gónzalez-Rey, Mario Delgado, Michael Rosu-Myles, Pablo Menendez

Haematologica September 2018 : haematol.2018.196568; doi:10.3324/haematol.2018.196568

Funding information

Financial support for this work was obtained from: Health Canada (H4084-1 12281), The European Research Council (Co G-2014 -6 46903), the Spanish Ministry of Ecnonomy and Competitiveness (SAF-SAF2013-43065), the Government of Catalonia, the Spanish Cancer Association (AECC-CI-201 5), the FERO Foundation, the “Hay Esperanza” Foundation, the Instituto Carlos III (ISCII I/FEDER/ PI14-01191).  The work also received support from the “la Caixa Foundation.   Pablo Menéndez is an ICREA Research Professor and a Cell Therapy Cooperative Network (TERCEL) researcher.