A study published in *Nature* (2010) reveals that dysfunction in bone progenitor cells can lead to myelodysplasia and secondary leukemia. The research shows that deleting the miRNA processing enzyme Dicer1 in mesenchymal osteoprogenitors causes severe hematopoietic disorders, including features of human myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). These effects are microenvironment-dependent and involve specific cells in the osteolineage. The study also identifies the Shwachman-Bodian-Diamond Syndrome (SBDS) gene as a key player in this process, as its deletion in osteoprogenitors mimics the effects of Dicer1 deletion. The findings highlight the critical role of the bone marrow microenvironment in maintaining hematopoietic homeostasis and suggest that disruptions in this environment can initiate neoplastic disease. The study further demonstrates that the bone marrow microenvironment can induce clonal evolution of tumor cells, leading to the development of leukemia. The research underscores the importance of mesenchymal cells in regulating hematopoietic stem cell function and highlights the potential of targeting the bone marrow microenvironment as a therapeutic strategy for hematological disorders. The study also provides insights into the molecular mechanisms underlying the pathogenesis of MDS and AML, emphasizing the complex interplay between genetic and environmental factors in these diseases.A study published in *Nature* (2010) reveals that dysfunction in bone progenitor cells can lead to myelodysplasia and secondary leukemia. The research shows that deleting the miRNA processing enzyme Dicer1 in mesenchymal osteoprogenitors causes severe hematopoietic disorders, including features of human myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). These effects are microenvironment-dependent and involve specific cells in the osteolineage. The study also identifies the Shwachman-Bodian-Diamond Syndrome (SBDS) gene as a key player in this process, as its deletion in osteoprogenitors mimics the effects of Dicer1 deletion. The findings highlight the critical role of the bone marrow microenvironment in maintaining hematopoietic homeostasis and suggest that disruptions in this environment can initiate neoplastic disease. The study further demonstrates that the bone marrow microenvironment can induce clonal evolution of tumor cells, leading to the development of leukemia. The research underscores the importance of mesenchymal cells in regulating hematopoietic stem cell function and highlights the potential of targeting the bone marrow microenvironment as a therapeutic strategy for hematological disorders. The study also provides insights into the molecular mechanisms underlying the pathogenesis of MDS and AML, emphasizing the complex interplay between genetic and environmental factors in these diseases.