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Plasmablastic lymphoma (PBL) is a rare, aggressive type of B-cell non-Hodgkin lymphoma with the vast majority of patients responding poorly to treatment or progressing shortly thereafter. Cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) or CHOP-like regimens have disappointing results in this setting. We report a case of PBL arising in a previously diagnosed myelodysplastic/myeloproliferative (MDS/MPN) with ring sideroblasts and thrombocytopenia (RS-T), HIV-negative patient treated with the combination of CHOP and bortezomib. The patient achieved complete metabolic response, which has lasted one year, longer by far than would have been expected with the sole use of CHOP. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) comprise the majority of CTCL, a heterogenous group of non-Hodgkins lymphomas involving the skin. The CTCL’s resistance to chemotherapy and the lack of full understanding of their pathogenesis request further investigation. With the view of a more targeted therapy, we evaluated in vitro the effectiveness of bortezomib and methotrexate, as well as their combination in CTCL cell lines, regarding apoptosis induction. Our data are of clinical value and indicate that the bortezomib/methotrexate combinational therapy has an inferior impact on the apoptosis of CTCL compared to monotherapy, with bortezomib presenting as the most efficient treatment option for SS and methotrexate for MF. Using PCR arrays technology, we also investigated the alterations in the expression profile of genes related to DNA repair pathways in CTCL cell lines after treatment with bortezomib or methotrexate. We found that both agents, but mostly bortezomib, significantly deregulate a large number of genes in SS and MF cell lines, suggesting another pathway through which these agents could induce apoptosis in CTCL. Finally, we show that SS and MF respond differently to treatment, verifying their distinct nature and further emphasizing the need for discrete treatment approaches. [ABSTRACT FROM AUTHOR]

In the present study, the ability of the proteasome inhibitor bortezomib (BZ), an oxidative stress-inducing agent, to sensitize acute myeloid leukemia (AML) cells to decitabine (Dacogen®, DAC; a DNA methyltransferase inhibitor), in terms of cell viability and differentiation, was investigated. Kasumi-1 AML (M2) cells were treated with low-dose DAC (10, 50, 100, 200 or 400 nΜ), with or without BZ (10 nM). Apoptosis and the cell cycle were evaluated after 24 h of treatment through fluorescence-assisted cell sorting (FACS) with Annexin V/propidium iodide and DAPI staining, respectively. The expression levels of CD193, CD11b, CD13, CD14, CD15, CD16 and CD117 surface differentiation markers were evaluated by FACS after 6 days of treatment. The results indicated significant alterations in cell death and cell cycle phases in Kasumi-1 cells following DAC and BZ combination treatment compared to untreated cells and cells with single treatments. Low-dose DAC/BZ combinations significantly enhanced apoptosis and decreased the population of live Kasumi-1 cells, with 100 and 200 nM of DAC and 10 nM BZ appearing to have the most potent synergistic effect according to a combination index. Furthermore, cell cycle profiling revealed that DAC/BZ treatment synergistically led to G0/G1- and G2/M-phase arrest. By contrast, DAC appeared to promote monocytic and granulocytic differentiation of Kasumi-1 cells more effectively alone than in combination with BZ. BZ acted synergistically with low-dose DAC in vitro, leading to enhanced apoptosis and G0/G1- and G2/M-phase arrest in AML cells, hence prohibiting either DNA synthesis or mitosis. Although further in vivo investigation is necessary, these results provide a strong rationale for the implementation of a combination treatment with DAC and bortezomib in AML therapy, followed by DAC alone, which may achieve better clinical responses and possibly partially overcome the frequently encountered DAC resistance of patients with AML. [ABSTRACT FROM AUTHOR]