Acute myelogenous leukemia blasts contribute to a bone marrow-stroma in in vivo NOD/SCID mouse system

Acute myelogenous leukemia (AML) blasts can convert to myofibroblasts to form stroma for the creation of a microenvironment to grow AML blasts in vivo. When non-adherent AML (M2) blast cells were transplanted into NOD/SCID mouse, cells were engrafted after 10 weeks. In the mouse bone marrow, human stromal cells were identified, in which RUNX-1 and ETO gene was fused with FISH analysis, and when the parental AML blasts were cultured on the expanded AML-derived myofibroblasts, AML cells grew extensively.
We reported previously that non-adherent AML cells differentiated into myofibroblasts to create a microenvironment for the proliferation of AML blasts in vitro. In this report we demonstrate that with severe combined immunodeficiency (SCID) mouse system AML blast cells also convert to myofibroblasts to form stroma in vivo.
Bone marrow cells from informed AML (M2) patients who had fusion chromosomal of RUNX-1 and ETO, from which non-adherent mononuclear cells were separated, and were injected to the 3.0 Gray-irradiated NOD)/SCID mouse intravenously. For the inactivation of NK cells, anti-Asialo GM1 antibody was injected intra-peritoneally prior to the transplantation, and on each 11th day thereafter. Blood was collected to monitor Runx1 and Eto fusion transcript, and mice were sacrificed after chimeric mRNA was observed. Bone marrow cells were obtained, sorted with anti-human CD133 antibody and -CD106 to select AML-derived human stromal myofibroblasts referred to the in vitro data. The isolated positive fraction was further cultured, and the biological and the molecular characteristics were analyzed.

When non-adherent AML (M2) blast cells were transplanted into NOD/SCID mouse, cells were engrafted after 10 weeks. In the mouse bone marrow cells, human stromal cells were identified, in which RUNX-1 and ETO gene was fused with FISH analysis. When the parental AML blast cells were cultured on the expanded AML-derived myofibroblasts, AML cells grew extensively.
Our results indicate that AML cells can create their own microenvironment for proliferation in vivo. It is possible that, when AML blasts differentiate into myofibroblasts, cell-fusion mechanism as well as the direct differentiation may work.

No relevant conflicts of interest declared.