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Hematology Frontier：
Myeloid malignancies are clonal disorders of the progenitor cells or hematopoietic stem cells. Could you discuss how cells in the bone marrow microenvironment influence the progression of these diseases and how we can use this knowledge to improve treatment strategies?
Professor Simón Méndez-Ferrer：
So actually, it was quite striking when people started examining the possibility that the cells that are not the mutant cells responsible for hematological diseases, but rather, the microenvironmental cells, might play a role in generating alterations in non-hematopoietic cells. These alterations were of different types, expressing molecules that were mutated in the case of germline mutations during hematological malignancies. But in other cases, they simply represented alterations in non-hematopoietic cells. And it was striking that in most of these experiments, the mouse models developed a type of disease that resembled myeloproliferative neoplasms. This suggests an important role for non-hematopoietic cells in the development of these diseases. This observation was made many years ago. Subsequently, researchers began to investigate which cells might be more important compared to others and found evidence that the niche could be an oncogenic inducer for the development of these malignancies.
However, most of the evidence for the role of the microenvironment actually stems from the consequences of mutations in hematopoietic cells, whereby the microenvironment becomes altered and stops functioning properly to support hematopoiesis, instead promoting the development of malignancy.
The alteration of the microenvironment can develop over many years. Some of these mutations are now detectable even before birth. Yet, patients typically manifest the disease associated with aging. Clearly, many factors are involved in the overall environment over the years that may contribute to the onset and progression of the disease. Therefore, now that this disease can be detected quite early, there is an opportunity for intervention and prevention of damage to the microenvironment, which may impede disease progression or enhance treatment effectiveness once the disease has developed.
