TY  - JOUR
AU  - Heckl, B.
AU  - Carlet, M.
AU  - Vick, B.
AU  - Roolf, C.*
AU  - Alsadeq, A.*
AU  - Grunert, M.
AU  - Liu, W.-H.
AU  - Liebl, A.
AU  - Hiddemann, W.*
AU  - Marschalek, R.*
AU  - Schewe, D.M.*
AU  - Spiekermann, K.*
AU  - Junghanss, C.*
AU  - Jeremias, I.
C1  - 54371
C2  - 45534
CY  - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
SP  - 848-851
TI  - Frequent and reliable engraftment of certain adult primary acute lymphoblastic leukemias in mice.
JO  - Leuk. Lymphoma
VL  - 60
IS  - 3
PB  - Taylor & Francis Ltd
PY  - 2019
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - Human metapneumovirus (hMPV) is an important cause of lower respiratory tract infection. In healthy subjects infections are usually mild and rarely necessitate hospitalization. However, more serious outcomes have been described for allogeneic stem cell transplant recipients. This study reports an outbreak of hMPV A2 infection in severely immunocompromised adult hematologic cancer patients in a tertiary care unit. HMPV RNA was detected in bronchoalveolar lavage or produced sputum from patients presenting with typical clinical features. A total of 15 patients were diagnosed in a period of 7 weeks. Molecular subtyping revealed infection with genotype A2a virus, implicating nosocomial transmission. Eleven patients (73%) were treated with intravenous immunoglobulins and ribavirin. Ten patients (65%) presented with severe dyspnea, five (33%) required mechanical ventilation. Four patients (26.6%) died from hMPV-associated pneumonia and consequent multi-organ failure. Thus, hMPV is a critical pathogen for patients with hematologic cancers warranting early detection.
AU  - Hoellein, A.*
AU  - Hecker, J.*
AU  - Hoffmann, D.
AU  - Göttle, F.*
AU  - Protzer, U.
AU  - Peschel, C.*
AU  - Götze, K.*
C1  - 47399
C2  - 39293
CY  - Abingdon
SP  - 623-627
TI  - Serious outbreak of human metapneumovirus in patients with hematologic malignancies.
JO  - Leuk. Lymphoma
VL  - 57
IS  - 3
PB  - Taylor & Francis Ltd
PY  - 2016
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - Lately, mTOR inhibitors have gained clinical relevance in malignant lymphoma. Still, rapamycin derivatives may activate a pro-survival feedback loop through PI3K-Akt. In this current study, temsirolimus effectively reduced cell growth in GCB and ABC diffuse large cell B-cell lymphoma (GCB = 30–66%, ABC = 45–57%). Combination treatment with the PI3K-δ inhibitor idelalisib additively effected ABC and GCB lymphoma (GCB = 16–38%, ABC = 25–50%). Since Bruton's Tyrosine Kinase (BTK) plays a significant role for the survival of ABC lymphoma, this study also combined the BTK inhibitor ibrutinib with temsirolimus, which resulted in additive cell growth reduction (ibrutinib 50%, temsirolimus 44%, combination 25%) in ABC lymphoma. In contrast, bortezomib, which has been shown previously to be efficient in ABC lymphoma, revealed an antagonistic effect with temsirolimus in some GCB lymphoma (temsirolimus 53%, temsirolimus + bortezomib 63%). Western blot analysis identified the increase of phosphorylated pro-survival kinases Akt and PDK as a possible underlying mechanism of this interaction.
AU  - Zoellner, A.-K.
AU  - Bayerl, S.
AU  - Hutter, G.
AU  - Zimmermann, Y.
AU  - Hiddemann, W.
AU  - Dreyling, M.
C1  - 46676
C2  - 37670
SP  - 3393-3400
TI  - Temsirolimus inhibits cell growth in combination with inhibitors of the B-cell receptor pathway.
JO  - Leuk. Lymphoma
VL  - 56
IS  - 12
PY  - 2015
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL displays an aggressive course, with a continuous relapse pattern and a median survival of only 3-7 years. However, a subset of up to 15% long-term survivors has recently been identified with a rather indolent clinical course. In general, conventional chemotherapy is only palliative and the median duration of remissions is only 1-2 years. In 2000, the European MCL Network (http://www.european-mcl.net) was founded, which consists of 15 national lymphoma study groups supplemented by experts in hematopathology, cytogenetics and molecular genetics. During the last decade, the European consortium has successfully initiated the largest phase III trials in MCL worldwide. In the current study generation, the addition of high dose cytosine arabinoside (Ara-C) to an R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival. Similarly, in elderly patients, rituximab maintenance until progression led to a marked prolongation of remission duration. Emerging strategies include proteasome inhibitors, immune modulatory drugs (IMiDs), mammalian target of rapamycin (mTOR) inhibitors and others, all based on the dysregulated cell cycle machinery and impairment of several signaling transduction and apoptotic pathways. Future strategies will apply individualized approaches according to the molecular risk profile of the patient. At the annual conference in Lisbon, recent results of molecular pathogenesis, analyses of current clinical trials and new study concepts were discussed.
AU  - Dreyling, M.*
AU  - Kluin-Nelemans, H.C.*
AU  - Beà, S.*
AU  - Klapper, W.*
AU  - Vogt, N.*
AU  - Delfau-Larue, M.H.*
AU  - Hutter, G.
AU  - Cheah, C.*
AU  - Chiappella, A.*
AU  - Cortelazzo, S.*
AU  - Pott, C.*
AU  - Hess, G.*
AU  - Visco, C.*
AU  - Vitolo, U.*
AU  - Klener, P.*
AU  - Aurer, I.*
AU  - Unterhalt, M.*
AU  - Ribrag, V.*
AU  - Hoster, E.*
AU  - Hermine, O.*
C1  - 24543
C2  - 31579
SP  - 699-707
TI  - Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma: Report of the 11th annual conference of the European Mantle Cell Lymphoma Network.
JO  - Leuk. Lymphoma
VL  - 54
IS  - 4
PB  - Informa Healthcare
PY  - 2013
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - We recently identified the marginal zone B and B1 cellspecific protein ( MZB1 ) as part of a gene expression signature associated with outcomes in chronic lymphocytic leukemia (CLL). MZB1 is important for B cell function as a key regulator of antibody secretion, calcium homeostasis and adhesion. Therefore, we analyzed the role of MZB1 expression levels in 139 patients with CLL using quantitative real-time polymerase chain reaction (qRT-PCR) and microarray data sets in CLL, follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM) and acute myeloid leukemia (AML). High MZB1 expression was associated with inferior survival in CLL (hazard ratio [HR]: 1.63 [confidence interval (CI): 1.14 – 2.33], p  0.007), FL (221286_s_at HR: 1.16 [CI: 0.98 – 1.37], p  0.086; 223565_at: HR: 1.3 [CI: 1.1 – 1.61], p  0.015) and DLBCL (221286_s_at: HR: 1.17 [CI: 1.06 – 1.3], p  0.003; 223565_at: HR: 1.21 [CI: 1.08 – 1.35], p  0.001). In DLBCL MZB1 expression was an additive prognostic marker in a multivariate model including activated B-cell like (ABC) versus germinal center (GCB) subtype. Additionally, MZB1 expression correlated with a unique gene expression pattern. This study is the first to show that the expression level of a single gene has prognostic significance in different lymphoma subtypes. Due to its biological function, MZB1 may play a central role in B cell neoplasms and is a potential target for future therapeutic interventions.
AU  - Herold, T.
AU  - Mulaw, M.A.
AU  - Jurinovic, V.*
AU  - Seiler, T.
AU  - Metzeler, K.H.*
AU  - Dufour, A.*
AU  - Schneider, S.*
AU  - Kakadia, P.M.
AU  - Spiekermann, K.
AU  - Mansmann, U.*
AU  - Hiddemann, W.
AU  - Buske, C.*
AU  - Dreyling, M.
AU  - Bohlander, S.K.
C1  - 11691
C2  - 30747
SP  - 1652-1657
TI  - High expression of MZB1 predicts adverse prognosis in chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma and is associated with a unique gene expression signature.
JO  - Leuk. Lymphoma
VL  - 54
IS  - 8
PB  - Informa Healthcare
PY  - 2013
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - Abstract Antileukemic-T-cell-responses, induced by leukemia-derived-dendritic-cells (DC(leu)) are variable, due to varying DC/DC(leu)-composition/quality. We studied DC/DC(leu)-composition/quality after blast-culture in four DC-media by flowcytometry (FC) and combined FISH/immunophenotyping-analysis(FISH-IPA). Both methods showed, that DC-methods produce variable proportions of DC-subtypes. 1)FISH-IPA is an elaborate method to study clonal aberrations in blast/DC-cells on slides, however without preselection of distinct cell-populations for FISH-analysis. 2)FISH-IPA-data proved previous FC-data: not every clonal/blast cell is converted to DC(leu) (resulting in various proportions of DC(leu)) and not every detectable DC is of clonal/leukemic origin. 3)Preselection of the best of four DC-methods for 'best' DC/DC(leu)-generation is necessary. 4)DC(leu)-proportions correlate with the antileukemic functionality of DC/DC(leu)-stimulated T-cells, thereby proving the necessity of studying quality of DC/DC(leu) after culture. 5)FC is the superior method to quantify DC/DC(leu), since a blast-phenotype is available in every given patient, even with low/no proportions of clonal aberrations, and can easily be used to study cellular compositions after DC-culture.
AU  - Kremser, A.*
AU  - Kufner, S.*
AU  - Konhaeuser, E.
AU  - Kroell, T.*
AU  - Hausmann, A.*
AU  - Tischer, J.*
AU  - Kolb, H.-J.*
AU  - Zitzelsberger, H.
AU  - Schmetzer, H.M.
C1  - 11184
C2  - 30540
SP  - 1297-1308
TI  - Combined immunophenotyping and fish ('Fish-Ipa') with chromosome-specific DNA-probes allows the quantification and differentation of ex vivo generated dendritic cells (DC), leukemia-derived DC and clonal leukemic cells in patients with AML.
JO  - Leuk. Lymphoma
VL  - 54
IS  - 6
PB  - Informa Healthcare
PY  - 2013
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. However, recently a subset of up to 15% long-term survivors has been identified with a rather indolent clinical course. Advanced stage disease is usually apparent already at first clinical manifestation; in general, conventional chemotherapy is only palliative and median duration of remissions is only 1-2 years. In 2000, the European MCL Network ( http://www.european-mcl.net ) was founded, which consists of 15 national lymphoma study groups supplemented by experts in hematopathology, cytogenetics and molecular genetics. During the last decade, the European consortium has successfully initiated the largest phase III trials in MCL worldwide. In the current study generation, the addition of high-dose Ara-C to a rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival. Similarly, in elderly patients, rituximab maintenance until progression led to a marked prolongation of remission duration. Emerging strategies include proteasome inhibitors, immune modulatory drugs (IMiDs), mammalian target of rapamycin (mTOR) inhibitors and others, all based on the dysregulated control of cell cycle machinery and impairment of several apoptotic pathways. Combination strategies are currently being investigated in numerous trials, but their introduction into clinical practice and current treatment algorithms remains a challenge. Future strategies will apply individualized approaches according to the molecular risk profile of the patient. At the annual conference in Warsaw, recent results of molecular pathogenesis, analyses of current clinical trials and new study concepts were discussed.
AU  - Dreyling, M.*
AU  - Kluin-Nelemans, H.C.*
AU  - Beà, S.*
AU  - Hartmann, E.*
AU  - Salaverria, I.*
AU  - Hutter, G.
AU  - Perez-Galan, P.*
AU  - Roue, G.*
AU  - Pott, C.*
AU  - Le Gouill, S.*
AU  - Cortelazzo, S.*
AU  - Rule, S.*
AU  - Hess, G.*
AU  - Zaja, F.*
AU  - Vitolo, U.*
AU  - Szymczyk, M.*
AU  - Walewski, J.*
AU  - Ribrag, V.*
AU  - Unterhalt, M.*
AU  - Hermine, O.*
AU  - Hoster, E*
AU  - European MCL Network (*)
C1  - 6908
C2  - 29413
CY  - London
SP  - 2226-2236
TI  - Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma: Report of the 10th annual conference of the European Mantle Cell Lymphoma Network.
JO  - Leuk. Lymphoma
VL  - 52
IS  - 12
PB  - Informa Healthcare
PY  - 2011
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - The aims of this study were to analyze the incidence and morphology of cyclin D1+ DLBCL and cases of Richter transformation (RT), and to elucidate possible molecular mechanisms of cyclin D1 overexpression. Seventy-two cases of de novo DLBCL and 12 cases of RT were included in this study. Cyclin D1 positivity was found in 10/66 (15%) cases of unselected de novo DLBCL and in 2/11 (18%) cases of RT. Seven independently identified cases of cyclin D1+ DLBCL, including one RT, were added to the study. Centroblastic morphology was found in 17/19 (89%) cases of cyclin D1+, most with a post-germinal center phenotype (CD10-, BCL6+, MUM1+). No alterations in the CCND1 gene indicative for a translocation t(11;14) were identified by FISH. Analysis of the MYC locus yielded gene copy alterations in five cases and no disruption of the gene locus in any case, suggesting an alternative mechanism of cyclin D1 deregulation.
AU  - Vela-Chávez, T.*
AU  - Adam, P.*
AU  - Kremer, M.*
AU  - Bink, K.
AU  - Bacon, C.M.*
AU  - Menon, G.*
AU  - Ferry, J.A.*
AU  - Fend, F.*
AU  - Jaffe, E.S.*
AU  - Quintanilla-Martinez, L.
C1  - 6466
C2  - 28744
SP  - 458-466
TI  - Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in the CCND1 gene locus.
JO  - Leuk. Lymphoma
VL  - 52
IS  - 3
PB  - Informa Healthcare
PY  - 2011
SN  - 1042-8194
ER  - 

TY  - JOUR
AB  - To determine the impact of imatinib therapy prior to allogeneic stem-cell transplantation in advanced stage chronic myelogenous leukaemia (CML), 30 CML patients who had received imatinib as part of pre-transplant treatment were analysed, with special emphasis on the cytogenetic response to imatinib therapy shortly before transplantation. Median patient age was 51 years (range, 24 - 64). At the time of transplantation all patients were in second or higher chronic phase (CP). The median follow-up after allogeneic transplantation was 360 days (range, 24 - 1524). Cox regression analysis revealed that the quality of cytogenetic response was a prognostic factor for transplant-related mortality (p = 0.050), relapse incidence (p = 0.015), leukaemia-free survival (p = 0.002) and overall survival (p = 0.006). A cytogenetic response with <35%BCR-ABL-positive interphase nuclei in FISH analysis from bone marrow was associated with a probability of overall survival of 81% at 3 years. In conclusion, our data suggest that advanced stage CML has an excellent outcome after allogeneic haematopoietic stem-cell transplantation when transplanted in the phase of cytogenetic response to imatinib.
AU  - Weisser, M.*
AU  - Schleuning, M.*
AU  - Haferlach, C.*
AU  - Schwerdtfeger, R.*
AU  - Kolb, H.-J.
C1  - 4024
C2  - 24953
SP  - 295-301
TI  - Allogeneic stem-cell transplantation provides excellent results in advanced stage chronic myeloid leukemia with major cytogenetic response to pre-transplant imatinib therapy.
JO  - Leuk. Lymphoma
VL  - 48
IS  - 2
PB  - Informa Healthcare
PY  - 2007
SN  - 1042-8194
ER  - 

TY  - JOUR
AU  - Kobrin, C.*
AU  - Cha, S.-C.*
AU  - Qin, H.*
AU  - Raffeld, M.*
AU  - Fend, F.
AU  - Quintanilla-Martinez, L.
AU  - Grove, S.*
AU  - Jaffe, E.S.*
AU  - Kwak, L.W.*
C1  - 3678
C2  - 23765
SP  - 1523-1534
TI  - Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas: Implications for lymphomagenesis.
JO  - Leuk. Lymphoma
VL  - 47
IS  - 8
PY  - 2006
SN  - 1042-8194
ER  - 

TY  - JOUR
AU  - Poleck-Dehlin, B.*
AU  - Duell, T.*
AU  - Bartl, R.*
AU  - Lohse, P.*
AU  - Rhein, A.*
AU  - Diebold, J.*
AU  - Kohl, P.*
AU  - Mittermüller, J.
C1  - 5233
C2  - 23194
SP  - 1905-1911
TI  - Genetic Analyses Permit the Differentiation between Reactive Malfunctions ("Promyelocyte Arrest") and Arising Promyelocyte Leukemia in a Pregnant Patient with a History of a Medullablastoma.
JO  - Leuk. Lymphoma
VL  - 45
PY  - 2004
SN  - 1042-8194
ER  - 

TY  - JOUR
AU  - Wendtner, C.-M.
AU  - Kofler, D.M.
AU  - Mayr, C.
AU  - Bund, D.
AU  - Hallek, M.
C1  - 1904
C2  - 22402
SP  - 897-904
TI  - The potential of gene transfer into primary B-CLL cells using recombinant virus vectors.
JO  - Leuk. Lymphoma
VL  - 45
PY  - 2004
SN  - 1042-8194
ER  -