Macrophage Inhibitory Factor-1 (MIF-1) controls the plasticity of multiple myeloma tumor cells.

Multiple Myeloma (MM) is the second most common hematological malignancy with a median survival of 5-10 years. While current treatments initially cause remission, relapse almost always occurs, leading to the hypothesis that a chemotherapy-resistant cancer stem cell (CSC) remains dormant, and undergoes self-renewal and differentiation to reestablish disease. Our finding is that the mature cancer cell (CD138+, rapidly proliferating and chemosensitive) has developmental plasticity; namely, the ability to dedifferentiate back into its own chemoresistant CSC progenitor, the CD138-, quiescent pre-plasma cell.

Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101.

Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, primarily due to the treatment-refractory/resistant nature of the disease. A rational approach to this compelling challenge is to develop new drugs that act synergistically with existing effective agents. This approach will reduce drug concentrations, avoid treatment resistance, and also improve treatment effectiveness by targeting new and nonredundant pathways in MM.

Cells isolated from bone-marrow and lungs of allergic BALB/C mice and cultured in the presence of IL-5 are respectively resistant and susceptible to apoptosis induced by dexamethasone.

We have previously reported that, in IL-5-stimulated bone-marrow cultures, dexamethasone upregulates eosinophil differentiation and protects developing eosinophils from apoptosis induced by a variety of agents. Recently developed procedures for the isolation of hemopoietic cells from allergic murine lungs have enabled us to evaluate how these cells respond to dexamethasone in IL-5-stimulated cultures, when compared with bone-marrow-derived cells isolated from the same donors, and whether differences in response patterns were linked to apoptosis. Ovalbumin challenge of sensitized mice increased significantly the numbers of mature leukocytes as well as hemopoietic cells recovered from digested lung fragments, relative to saline-challenged, sensitized controls.

Isolation and characterization of hemopoietic cells from lungs of allergic mice.

We developed a procedure for the isolation of hemopoietic cells from murine lung. Ovalbumin sensitization and challenge increased the numbers of functionally intact hemopoietic progenitors recovered from digested lung fragments by 80-fold to 120-fold, relative to naive controls. Eosinophil precursors, which are absent in the naive mouse lung, accumulated in the lungs of sensitized/challenged mice.

Allergenic sensitization prevents upregulation of haemopoiesis by cyclo-oxygenase inhibitors in mice.

1. We evaluated whether immunization affects bone-marrow responses to indomethacin, because allergenic sensitization and challenge upregulate responses to haemopoietic cytokines (including IL-5-driven eosinopoiesis) in murine bone-marrow, while indomethacin upregulates haemopoiesis and protects bone-marrow from radiation damage. 2.