An extracellular matrix signature in leukemia precursor cells and acute myeloid leukemia.

Despite major therapeutic advancements, worldwide death rates of acute myeloid leukemia (AML) remain high, with approximately 20,830 people diagnosed in the USA in 2015, 10,460 (50.21%) of whom were estimated to die from the disease. Several studies have shown that leukemia stem cells (LSCs), the founder cells from which AML arise, are characterized by specific transcriptional and epigenetic profiles which can be applied to predict patient survival and prognosis. The actual model for AML development postulates that LSC arise within the same niches as the normal hematopoietic stem cells (HSCs), taking them over in time as the hematopoietic niche turns into a leukemic niche. While the altered expression of different extracellular matrix (ECM) elements within the leukemic niche has already been investigated, the direct contribution of LSCs to the modification of the niche ECM has not been assessed systematically, and the prognostic relevance of alterations to the ECM homeostasis directly operated by LSCs, and AML cells remains untested. To this aim, we studied the transcriptional profile of ECM-related genes in LSCs, and applied the results to two AML cohorts to verify their prognostic potential. The raw microarray profiles of normal HSCs, multipotent progenitors (MPPs), committed progenitors (megakaryocyte-erythrocyte progenitors, MEPs, common myeloid progenitors, CMPs, and granulocyte/monocyte progenitors, GMPs), LSCs, leukemia progenitor cells