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Jesper Jurlander

Publications and source records attributed to Jesper Jurlander.

4 recordsLinked to original sources
PubMed2003

The in vivo profile of transcription factors during neutrophil differentiation in human bone marrow.

In vivo distribution of myeloid transcription factors during granulopoiesis was investigated by Northern and Western blotting in 3 neutrophil precursor populations from human bone marrow: immature (myeloblasts [MBs] and promyelocytes [PMs]); intermediate mature (myelocytes [MCs] and metamyelocytes [MMs]); and mature neutrophil cells (band cells [BCs] and segmented neutrophil cells [SCs]). Nonneutrophil cells were removed with magnetic-bead-coupled antibodies against CD2, CD3, CD14, CD19, CD56, CD61, glycophorin-A, and CD49d (BCs/SCs) before RNA and protein extraction. Polymorphonuclear neutrophils (PMNs) from peripheral blood depleted with anti-CD49d antibodies were also included. Expression of acute myeloid leukemia 1b (AML-1b), c-myb, GATA-1, and CCAAT/enhancer binding protein gamma (C/EBP-gamma) was seen primarily in MBs/PMs, and little expression was found in more mature cells. The level of C/EBP-alpha was constant in the bone marrow-derived cells and decreased in PMNs. C/EBP-epsilon was found primarily in MCs/MMs and was almost absent in more mature cells. Expression of C/EBP-beta, C/EBP-delta, and C/EBP-zeta was observed from the MC/MM stage onward, with peak levels in the most mature cells. The amount of PU.1 increased throughout maturation whereas the level of Elf-1 reached a nadir in MCs/MMs The PU.1 coactivator c-jun and c-jun's dimerization partner c-fos were both detectable in MCs/MMs and increased in amount with maturity. CCAAT displacement protein (CDP) was found at comparable levels at all stages of differentiation. This demonstrates a highly individualized expression of the transcription factors, which can form the basis for the heterogeneous expression of granule proteins during granulopoiesis and cell cycle arrest in metamyelocytes.

Antigens, CD↗
PubMed2003

How myeloma cells escape bisphosphonate-mediated killing: development of specific resistance with preserved sensitivity to conventional chemotherapeutics.

Although amino-bisphosphonates (N-BPs) induce apoptosis of myeloma cells in vitro, most in-vivo studies fail to demonstrate a corresponding antitumour effect. This discrepancy might reflect the development of resistance to the antitumour effects of N-BP in myeloma cells when they are exposed to N-BP for a prolonged time. To test this hypothesis, two N-BP-sensitive human myeloma cell lines were continuously exposed to increasing concentrations of the N-BP alendronate for 6 weeks. During this treatment period, 10 out of 10 sublines developed reduced apoptotic and antiproliferative responses to alendronate treatment. This de novo alendronate resistance was accompanied by resistance to another N-BP (zoledronate) but not to an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase or Fas ligand. Importantly, N-BP-resistant myeloma cells also remained sensitive to conventional myeloma chemotherapeutics (melphalan, doxorubicin and vincristine). Further analysis of the N-BP-resistant cells revealed an increased activity of the N-BP-specific target enzyme farnesyl pyrophosphate synthase, without upregulation of its gene transcription. Our results suggest that continuous exposure of myeloma cells to alendronate leads to the development of N-BP resistance. This is associated with an increased activity of farnesyl pyrophosphate synthase and does not evolve from defective apoptotic pathways. Importantly, the antitumour effects of conventional myeloma chemotherapeutics are preserved in the N-BP-resistant myeloma cells.

Alendronate↗
PubMed2002

The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism.

Antibodies against CD20 can activate complement and induce antibody-dependent cellular cytotoxicity (ADCC) in B lymphocytes. In B-cell lines, such antibodies also induce apoptosis. In this study, the expression and function of CD20 on B-cell chronic lymphocytic leukemia (B-CLL) cells were analyzed. Flow cytometric analysis demonstrated that B-CLL cells express CD20 with a fluorescence intensity that is significantly weaker than that of normal CD5(+) and CD5(-) B cells and that of malignant CD5(-) low-grade non-Hodgkin lymphoma cells. A small population of cells from healthy donors that have an expression pattern of CD5 and CD20 identical to that of B-CLL cells were identified, and this population was confirmed to be of T lineage, not B lineage. Culture of freshly isolated B-CLL cells in the presence of the chimeric anti-CD20 antibody rituximab and a cross-linking F(ab)(2) fragment, resulted in dose- and time-dependent induction of apoptosis. The induction of apoptosis occurred under conditions in which the influence of complement activation and ADCC was negligible. Cross-linking of rituximab induced strong and sustained phosphorylation of the 3 mitogen activated protein (MAP) kinases c-Jun NH2-terminal protein kinase, extracellular signal-regulated kinase, and p38. Introduction of the p38 inhibitor SB203580 into the system completely blocked signaling downstream of p38, as evidenced by the absence of MAPKAP K2 activity, and significantly reduced the degree of anti-CD20-induced apoptosis. These results demonstrate that cross-linking of rituximab bound to CD20 on freshly isolated B-CLL cells induces apoptosis through a signaling pathway that is dependent on p38 MAP-kinase activation.

Antibodies, Monoclonal↗