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181 results on '"Thunberg, U."'

12. O-014 High BRAF mutation frequency and marked survival differences in subgroups according to KRAS/BRAF mutation status and tumor tissue availability in a prospective population-based metastatic colorectal cancer cohort

Author

Sorbye, H., primary, Dragomir, A., additional, Sundstrom, M., additional, Pfeiffer, P., additional, Thunberg, U., additional, Bergfors, M., additional, Aasebo, K., additional, Eide, G., additional, Ponten, F., additional, Qvortrup, C., additional, and Glimelius, B., additional

Published
2015
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14. Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas

Author

Walsh, S.H., Grabowski, P., Berglund, M., Thunberg, U., Thorselius, M., Tobin, G., Aleskog, A., Karlsson, Katarina, Sundstrom, C., Laurell, A., Enblad, G., Rosenquist, R., Roos, G., Walsh, S.H., Grabowski, P., Berglund, M., Thunberg, U., Thorselius, M., Tobin, G., Aleskog, A., Karlsson, Katarina, Sundstrom, C., Laurell, A., Enblad, G., Rosenquist, R., and Roos, G.

Abstract

Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin. © 2007 The Authors.

Published
2007
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15. The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia.

Author

Skogsberg, S, Tobin, G, Kröber, A, Kienle, D, Thunberg, U, Åleskog, Anna, Karlsson, K, Laurell, A, Merup, M, Vilpo, J, Sundström, C, Roos, G, Jernberg-Wiklund, H, Döhner, H, Nilsson, K, Stilgenbauer, S, Rosenquist, R, Skogsberg, S, Tobin, G, Kröber, A, Kienle, D, Thunberg, U, Åleskog, Anna, Karlsson, K, Laurell, A, Merup, M, Vilpo, J, Sundström, C, Roos, G, Jernberg-Wiklund, H, Döhner, H, Nilsson, K, Stilgenbauer, S, and Rosenquist, R

Published
2006

16. The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia

Author

Skogsberg, A., Tobin, G., Krober, A., Kienle, D., Thunberg, U., Aleskog, A., Karlsson, K., Laurell, A., Merup, M., Vilpo, J., Sundstrom, C., Roos, G., Jernberg-Wiklund, H., Dohner, H., Nilsson, K., Stilgenbauer, S., Rosenquist, R., Skogsberg, A., Tobin, G., Krober, A., Kienle, D., Thunberg, U., Aleskog, A., Karlsson, K., Laurell, A., Merup, M., Vilpo, J., Sundstrom, C., Roos, G., Jernberg-Wiklund, H., Dohner, H., Nilsson, K., Stilgenbauer, S., and Rosenquist, R.

Abstract

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL. © 2006 Nature Publishing Group All rights reserved.

Published
2006
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17. Strikingly homologous immunoglobulin gene rearrangements and poor outcome inV(H)3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status

Author

Thorselius, M, Krober, A, Murray, F, Thunberg, U, Tobin, G, Buhler, A, Kienle, D, Albesiano, E, Maffei, R, Dao-Ung, LP, Wiley, J, Vilpo, J, Laurell, A, Merup, M, Roos, G, Karlsson, K, Chiorazzi, N, Marasca, R, Dohner, H, Stilgenbauer, S, Rosenquist, R, Thorselius, M, Krober, A, Murray, F, Thunberg, U, Tobin, G, Buhler, A, Kienle, D, Albesiano, E, Maffei, R, Dao-Ung, LP, Wiley, J, Vilpo, J, Laurell, A, Merup, M, Roos, G, Karlsson, K, Chiorazzi, N, Marasca, R, Dohner, H, Stilgenbauer, S, and Rosenquist, R

Abstract

We recently reported that Swedish V(H)3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite V-H mutation status. To investigate this further, we analyzed the V-H and V-L gene rearrangements in 90 V(H)3-21(+) patients from Sweden, Germany, Italy, United States, Finland, and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated V-H genes and 37% unmutated V-H genes. Fifty (56%) patients displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif DANGMDV. Also, a highly biased V(lambda)2-14 use was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although V(H)3-21(+) CLILs have a remarkably predominant X expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the V(H)3-21(+) cohort (median survival, 88 months), with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated VH3-21(+) cases as well as a slight increase of 11q- aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize VH3-21(+) CLLs independent of geographic origin and mutation status.

Published
2006
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25. Mutated VH genes and preferential VH3-21 use define new subsets of mantle cell lymphoma

Author

Walsh, SH, Thorsélius, M, Johnson, A, Söderberg, O, Jerkeman, M, Björck, E, Eriksson, I, Thunberg, U, Landgren, O, Ehinger, M, Löfvenberg, E, Wallman, K, Enblad, G, Sander, B, Porwit-MacDonald, A, Dictor, M, Olofsson, T, Sundström, C, Roos, G, Rosenquist, R, Walsh, SH, Thorsélius, M, Johnson, A, Söderberg, O, Jerkeman, M, Björck, E, Eriksson, I, Thunberg, U, Landgren, O, Ehinger, M, Löfvenberg, E, Wallman, K, Enblad, G, Sander, B, Porwit-MacDonald, A, Dictor, M, Olofsson, T, Sundström, C, Roos, G, and Rosenquist, R

Published
2003

27. Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia : clinical and biological implications.

Author

Hultdin, M, Rosenquist, R, Thunberg, U, Tobin, G, Norrback, K-F, Johnson, A, Sundström, C, Roos, G, Hultdin, M, Rosenquist, R, Thunberg, U, Tobin, G, Norrback, K-F, Johnson, A, Sundström, C, and Roos, G

Abstract

The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (>6%) had long telomeres ( approximately 8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.

Published
2003
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28. Somatic hypermutation and V(H) gene usage in mantle cell lymphoma.

Author

Thorselius, M, Walsh, S, Eriksson, I, Thunberg, U, Johnson, A, Backlin, C, Enblad, G, Sundstrom, C, Roos, G, Rosenquist, R, Thorselius, M, Walsh, S, Eriksson, I, Thunberg, U, Johnson, A, Backlin, C, Enblad, G, Sundstrom, C, Roos, G, and Rosenquist, R

Published
2002

39. The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia

Author

Skogsberg, Å, primary, Tobin, G, additional, Kröber, A, additional, Kienle, D, additional, Thunberg, U, additional, Åleskog, A, additional, Karlsson, K, additional, Laurell, A, additional, Merup, M, additional, Vilpo, J, additional, Sundström, C, additional, Roos, G, additional, Jernberg-Wiklund, H, additional, Döhner, H, additional, Nilsson, K, additional, Stilgenbauer, S, additional, and Rosenquist, R, additional

Published
2005
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40. Linear reduction of clonal cells in stem cell enriched grafts intransplanted multiple myeloma.

Author

Thunberg, U, Banghagen, M, Bengtsson, M, Christensen, LD, Geisler, CH, Gimsing, P, Lenhoff, S, Mortensen, BT, Olofsson, T, Simonsson, B, Andersen, NS, Sundstrom, C, Swedin, A, Sallstrom, JF, Thuresson, B, Westin, J, Carlson, K, Thunberg, U, Banghagen, M, Bengtsson, M, Christensen, LD, Geisler, CH, Gimsing, P, Lenhoff, S, Mortensen, BT, Olofsson, T, Simonsson, B, Andersen, NS, Sundstrom, C, Swedin, A, Sallstrom, JF, Thuresson, B, Westin, J, and Carlson, K

Published
1999

44. Linear reduction of clonal cells in stem cell enriched grafts in transplanted multiple myeloma

Author

Thunberg, U, Bånghagen, M, Bengtsson, M, Christensen, LD, Geisler, CH, Gimsing, P, Lenhoff, S, Mortensen, BT, Olofsson, T, Simonsson, B, Andersen, NS, Sundström, C, Swedin, A, Sällström, JF, Thuresson, B, Westin, J, Carlson, K, Thunberg, U, Bånghagen, M, Bengtsson, M, Christensen, LD, Geisler, CH, Gimsing, P, Lenhoff, S, Mortensen, BT, Olofsson, T, Simonsson, B, Andersen, NS, Sundström, C, Swedin, A, Sällström, JF, Thuresson, B, Westin, J, and Carlson, K

Published
1999

45. Clonal evolution as judged by immunoglobulin heavy chain gene rearrangements in relapsing precursor-B acute lymphoblastic leukemia.

Author

Rosenquist, R, Thunberg, U, Li, Aihong, Forestier, Erik, Lönnerholm, G, Lindh, Jack, Sundström, C, Sällström, J, Holmberg, D, Roos, Göran, Rosenquist, R, Thunberg, U, Li, Aihong, Forestier, Erik, Lönnerholm, G, Lindh, Jack, Sundström, C, Sällström, J, Holmberg, D, and Roos, Göran

Abstract

Oligoclonality and ongoing clonal evolution are common features in patients with precursor-B (pre-B) acute lymphoblastic leukemia (ALL), as judged by immunoglobulin heavy chain (IgH) gene rearrangement analysis. These features are considered to be results of secondary rearrangements after malignant transformation or emergence of new tumor clones. In the present study we analyzed the IgH gene rearrangement status in 18 cases with relapsing pre-B ALL using variable heavy chain (V(H)) gene family specific polymerase chain reaction (PCR) amplification and single stranded conformation polymorphism (SSCP) analysis. Clonal IgH rearrangements were displayed in all leukemias but one, and altered rearrangement patterns occurred in five cases (29%), which were selected for detailed nucleotide sequence analysis. In one case, multiple subclones at diagnosis were suggested to be derived from a progenitor clone through joining of different V(H) germline gene segments to a pre-existing D-J(H) complex (V(H) to D-J(H) joining). Evidence for V(H) gene replacement with identical N-sequences at the V(H)-D junction and a common D-J(H) region was observed in one case. Diversification at the V(H)-D junction consisting of heterogeneous N-sequences were observed in one case. This molecular modification of the V(H)-D region could fit a hypothesized "open-and-shut" mechanism. Nevertheless, despite these ongoing events at least one IgH rearrangement remained unchanged throughout the disease in most patients, indicating that the immunoglobulin heavy chain locus can be a suitable marker for detection of minimal residual disease (MRD).

Published
1999

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