Hematon: a multicellular functional unit in primary hematopoiesis.

Bone marrow aspirates from healthy donors contain a fraction of low density multicellular spheroids, 100-500 microns in diameter. They are organized in a three-dimensional network consisting of central preadipocytes/adipocytes, mesenchymal and reticular cells, and resident macrophages that are closely associated with myeloid, erythroid and megakaryocyte progenitor cells and with their progenies. These spheroids are 2- to 5- fold more abundant in progenitor cells compared with the whole bone marrow as estimated by monoclonal antibody markers My 10 and T 9, by analysis of granulocyte--macrophage colony forming cells (GM-CFC) and by cytological techniques. They produce terminally differentiated cells in organotypic microcultures. We suggest that a multicellular spheroid may represent the fundamental unit of primary hematopoiesis; we therefore name it hematon. Here we show that the presence of hematons in bone marrow aspirates correlated positively with homeostatic blood cell production: they were present in normal bone marrow (BM) (19/25), and absent in myelodysplasic syndromes (MDPS) (8/21), in acute nonlymphocytic leukemias (ANLL) (3/22) and in chronic myeloid leukemia (CML) (2/28). The hematons were recovered under hematological remission in MDPS and in ANLL, suggesting that they may be dispersed reversibly in certain disease conditions. The hematons represent a unifying model around which the variability in some bone marrow cell functions can be explored.