The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.

Flt3/flk-2 ligand (flt3-L) is a potent costimulator of normal bone marrow (BM) myeloid progenitors. Flt3-L is produced by BM stromal cells and its receptor is expressed in the majority of acute myeloid leukemia (AML) cases. Therefore, flt3-L may play a role in the paracrine and/or autocrine loops sustaining leukemic cell growth. We evaluated the effects of recombinant human flt3-L on proliferation, apoptosis, and Bcl-2 and Bax expression in primary AML cells and compared them with those of stem cell factor (SCF). Mononuclear BM cells from patients with newly diagnosed AML were cultured in serum-free conditions with flt3-L, SCF, granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-colony-stimulating factor (GM-CSF) alone and in combination. In 9 of 10 samples, flt3-L significantly increased [3H]thymidine uptake (geometric mean stimulation index, 7.5; range, 2.4 to 41.5). Flt3-L also increased the number of AML blast colonies by 126% (range, 61% to 181%). In these 9 samples, flt3-L significantly enhanced the proliferative response triggered by G-CSF or GM-CSF. Flt3- L prevented apoptosis in AML blasts. It reduced the number of apoptotic cells by 36% +/- 3.9% compared with control cultures. Combining flt3-L with G-CSF or GM-CSF doubled the antiapoptotic effect. Cellular Bcl-2 and Bax levels were determined separately for apoptotic and nonapoptotic cells by flow cytometry. Cells undergoing spontaneous apoptosis had low Bcl-2 and high Bax levels, whereas nonapoptotic cells had high Bcl-2 and low Bax levels. Flt3-L alone or in combination with G-CSF or GM-CSF did not upregulate Bcl-2. However, Bax expression decreased in viable cells in the presence of these cytokines and the lowest level was achieved when a combination of flt3 and GM-CSF was used. Proliferative and viability effects of flt3-L were similar to those of SCF. Our results demonstrate that flt3-L acts as a stimulatory factor for primary AML cells. The antiapoptotic effects of flt3-L or its combinations with G-CSF or GM-CSF correlate with their ability to prevent upregulation of Bax.

Background: To study the histological structure and immunohistochemical (IHC) parameters of the plasmacytoma tumour substrate in patients with multiple myeloma (MM). Methods: The study included 21 patients (10 men/11 women) aged 23 to 73 years old with newly diagnosed MM complicated by plasmacytoma. Bone plasmacytoma was diagnosed in 14 patients, and extramedullary plasmacytoma was diagnosed in 7 patients. Plasmacytoma tissue specimens were examined using a LEICA DM4000B microscope. Anti-CD56, anti-CD166, anti-CXCR4, anti-Ki-67, and anti-c-MYC antibodies were used for IHC study of plasmacytoma biopsies. Results: When comparing the morphology of bone and extramedullary plasmacytoma, no significant differences were revealed; however, the substrate of extramedullary plasmacytoma was more often represented by tumour cells with an immature morphology than was the bone plasmacytoma substrate (57.1% vs. 28.6%, respectively). We revealed a significant difference in the expression of CD166 between bone and extramedullary plasmacytoma. The mean values of CD166 expression in bone plasmacytoma cells were significantly higher (36.29 ± 7.61% versus 9.57 ± 8.46%, respectively; p = 0.033) than those in extramedullary plasmacytoma cells. We noticed that in extramedullary plasmacytoma cells, there were higher values for the Ki-67 index than in bone plasmacytoma cells, and this result was independent of cell morphology. Conclusion: The mechanisms involved in the dissemination of tumour plasma cells are currently unexplored. Even in such a small sample, some differences in expression could be identified, which may indicate that different mechanisms lead to the formation of bone and extramedullary plasmacytomas. Specifically, the expression of CD166 in extramedullary plasmacytoma cells was almost 4 times lower than that in bone plasmacytoma cells, which may indicate the involvement of CD166 in the mechanisms of bone destruction. The proliferative activity of extramedullary plasmacytoma cells was shown to be higher than that of bone plasmacytoma cells.

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