Myeloblasts Convert into Fibroblastoid Stromal Cells To Create a Microenvironment for Proliferation of Leukemia Blasts in Acute and Chronic Myelogenous Leukemia Cases.

Abstract

Object: Cancer stem cell has been analyzed in leukemia, which behaves similarly to normal stem cells on their self-renewal and self-conversion into abnormally differentiated cells to make an exact recapitulation of the original heterogeneous leukemia cells. We observed a primary in vitro culture of non-adherent leukemia blasts prepared from various kinds of acute leukemia and chronic myelogenous leukemia cases, and biological and biochemical characteristics were analyzed.Method: Leukemia blast-rich fractions were prepared from patients' blood or bone marrow after gradient sedimentation method, which were cultured for a long term. When the appearance of the cultured cells converted into fibroblastoid cells, cells were divided into clones, analyzed molecularly to identify whether they were originated from leukemia clone, and their histochemical, biochemical and functional characterizations were determined.Results: Morphological changes into fibroblastoid stromal cells were observed in AML with t (11; 19) (p23; p13.1), M4E, Ph-positive biphenotype and CML (chronic and myeloid blast phase) cases but neither in ALL nor in CML-lymphoid blast cases. The generated fibroblastoid cells had enough functions equal to those of the normal bone marrow fibroblasts on their molecular expression (CD106, fibronectin), production of cytokines (VEGF, IL-7) and giving the activity of proliferation to normal hematopoietic cells. These cells maintained their characteristics observed in the original leukemia blasts (expression of CD13, CD33 and myeloperoxidase), which cells also expressed CD 34 and 133. Leukemia blasts proliferated extensively when cultured on the expanded fibroblastoid cells derived from leukemia blasts.Discussion: These results indicate that leukemia blasts can create their own microenvironment for proliferation.