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Cell Biology International 04/2013; · 1.48 Impact Factor
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ABSTRACT: Background Myelofibrosis is a myeloproliferative stem cell disorder curable exclusively by allogeneic hematopoietic stem cell transplantation and is associated with substantial mortality and morbidity. The aim of this study was to assess disease-specific and transplant-related risk factors that influence post-transplant outcome in patients with myelofibrosis. DESIGN AND METHODS: We retrospectively assessed 76 consecutive patients with primary (n=47) or secondary (n=29) myelofibrosis who underwent bone marrow (n=6) or peripheral blood stem cell (n=70) transplantation from sibling (n=30) or unrelated (n=46) donors between January 1994 and December 2010. The median follow-up of surviving patients was 55±7.5 months. RESULTS: Primary graft failure occurred in 5% and the non-relapse mortality rate at 1 year was 28%. The relapse-free survival rate was 50% with a relapse rate of 19% at 5 years. The use of pharmacological pre-treatment and the post-transplant occurrence of chronic graft-versus-host disease were significant independent unfavourable risk factors for post-transplant survival in multivariate analysis. Using the Dynamic International Prognostic Scoring System for risk stratification, low-risk patients had significantly better overall survival (P=0.014, hazard ratio 1.4) and relapse-free survival (P=0.02, hazard ratio 1.3) compared to the other risk groups of patients. The additional inclusion of thrombocytopenia, abnormal karyotype and transfusion need (Dynamic International Prognostic Scoring System Plus) resulted in a predicted 5-year overall survival of 100%, 51%, 54% and 30% for low, intermediate-1, intermediate-2 and high-risk groups, respectively. The relapse incidence was significantly higher in the absence of chronic graft-versus-host disease (P=0.006), and pharmacological pre-treatment (n=43) was associated with reduced relapse-free survival (P=0.001). Conclusions The data corroborate a strong correlation between alloreactivity and long-term post-transplant disease control and confirm an inverse relationship between disease stage, pharmacotherapy and outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. The Dynamic International Prognostic Scoring System was demonstrated to be useful for risk stratification of patients with myelofibrosis who are to undergo hematopoietic stem cell transplantation.
Haematologica 04/2012; 97(10):1574-81. · 6.42 Impact Factor
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ABSTRACT: hCG hormone is a naturally occurring, immune-modulating agent, which is highly expressed during pregnancy and causes improvements of some autoimmune diseases such as multiple sclerosis and Crohn's disease. Little is known about its immune-modulating effects. This study in MNCs of women who received hCG as preconditioning prior to IVF demonstrates that hCG increases anti-inflammatory IL-27 expression and reduces inflammatory IL-17 expression. In addition, we found increased IL-10 levels and elevated numbers of Tregs in peripheral blood of women after hCG application. Rejection of allogeneic skin grafts was delayed in female mice receiving hCG. We conclude that hCG may be useful for the induction of immune tolerance in solid organ transplantation.
Journal of leukocyte biology 08/2011; 90(5):1017-26. · 4.99 Impact Factor
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Ahmet H Elmaagacli,
Nina K Steckel,
Michael Koldehoff,
Yael Hegerfeldt,
Rudolf Trenschel,
Markus Ditschkowski,
Sandra Christoph,
Tanja Gromke,
Lambros Kordelas,
Hellmut D Ottinger,
Rudolf S Ross,
Peter A Horn,
Susanne Schnittger,
Dietrich W Beelen
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ABSTRACT: The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.
Blood 05/2011; 118(5):1402-12. · 9.90 Impact Factor
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Annals of Hematology 01/2011; 90(1):117-8. · 2.62 Impact Factor
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Blood 04/2010; 115(17):3644-5; author reply 3645-6. · 9.90 Impact Factor
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ABSTRACT: Selective inhibition of the BCR-ABL tyrosine kinase by RNA interference has been demonstrated in leukemic cells. We, therefore, evaluated specific BCR-ABL small interfering RNA silencing in BCR-ABL-positive cell lines, including those resistant to imatinib and particularly those with the T315I mutation.
The factor-independent 32Dp210 BCR-ABL oligoclonal cell lines and human imatinib-resistant BCR-ABL-positive cells from patients with leukemic disorders were investigated. The effects of BCR-ABL small interfering RNA or the combination of BCR-ABL small interfering RNA with imatinib and nilotinib were compared with those of the ABL inhibitors imatinib and nilotinib.
Co-administration of BCR-ABL small interfering RNA with imatinib or nilotinib dramatically reduced BCR-ABL expression in wild-type and mutated BCR-ABL cells and increased the lethal capacity. BCR-ABL small interfering RNA significantly induced apoptosis and inhibited proliferation in wild-type (P<0.0001) and mutated cells (H396P, T315I, P<0.0001) versus controls. Co-treatment with BCR-ABL small interfering RNA and imatinib or nilotinib resulted in increased inhibition of proliferation and induction of apoptosis in T315I cells as compared to imatinib or nilotinib alone (P<0.0001). Furthermore, the combination of BCR-ABL small interfering RNA with imatinib or nilotinib significantly (P<0.01) reversed multidrug resistance-1 gene-dependent resistance of mutated cells. In T315I cells BCR-ABL small interfering RNA with nilotinib had powerful effects on cell cycle distribution.
Our data suggest that silencing by BCR-ABL small interfering RNA combined with imatinib or nilotinib may be associated with an additive antileukemic activity against tyrosine kinase inhibitor-sensitive and resistant BCR-ABL cells, and might be an alternative approach to overcome BCR-ABL mutations.
Haematologica 03/2010; 95(3):388-97. · 6.42 Impact Factor
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ABSTRACT: Within the recent years, RNA interference (RNAi) has become an almost-standard method for in vitro knockdown of any target gene of interest. Now, one major focus is to further explore its potential in vivo, including the development of novel therapeutic strategies. From the mechanism, it becomes clear that small interfering RNAs (siRNAs) play a pivotal role in triggering RNAi. Thus, the efficient delivery of target gene-specific siRNAs is one major challenge in the establishment of therapeutic RNAi. Here we show that in vivo application of targeted nonvirally delivered synthetic bcr-abl siRNA in a female patient with recurrent Philadelphia chromosome positive chronic myeloid leukemia (CML) resistant to imatinib (Y253F mutation) and chemotherapy after allogeneic hematopoietic stem cell transplantation can silence the expression of bcr-abl gene. We found a remarkable inhibition of the overexpressed bcr-abl oncogene resulting in increased apoptosis of CML cells. In vivo siRNA application was well tolerated without any clinically adverse events. Our findings imply that the clinical application of synthetic siRNA is feasible, safe and has real potential for genetic-based therapies using synthetic nonviral carriers.
Methods in molecular biology (Clifton, N.J.) 02/2009; 487:451-66.
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ABSTRACT: Angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma (MM), and MM cells secrete vascular endothelial growth factor (VEGF), which further promotes proliferation of the tumor cells. Therefore, we evaluated the anti-myeloma effect of VEGF small interfering RNA (siRNA) silencing in MM cells and whether it can be augmented by the additional application of bortezomib directed against the 26S proteasome. After transfection with VEGF siRNA, we observed a reduction of VEGF expression in all studied cell lines: OPM-2, RPMI-8226, INA-6, Jurkat, Raji, and Karpas-299, as well as in cells of MM and lymphoma patients. VEGF siRNA significantly induced apoptosis and inhibited proliferation in OPM-2 cells (P<0.0001), RPMI-8226 (P<0.0001), and INA-6 (P<0.01) versus controls. Cotreatment with VEGF siRNA and bortezomib in MM cells resulted in an exaggerated inhibition of proliferation and induction of apoptosis compared with VEGF siRNA or bortezomib alone (P<0.001). In addition, the combination of VEGF siRNA and bortezomib significantly (P<0.01) reversed multidrug resistance gene 1-dependent resistance of MM cells. Our data suggest that small-molecule inhibition of proteasome and silencing by VEGF-specific siRNA may be associated with an additive antitumor activity and might be a suitable target for new, therapeutic strategies using RNA interference in MM.
Journal of Leukocyte Biology 05/2008; 84(2):561-76. · 4.99 Impact Factor
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ABSTRACT: To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, the naturally Gfi-1B overexpressing cell line K562 was cultured in the presence of Gfi-1B target-specific small interfering RNA (siRNA). SiRNA treatment significantly knocked down Gfi-1B expression with an efficiency of nearly 90%. Analysis of the siRNA silencing protocol by colony-forming units ensured that it was not cytotoxic. Samples from Gfi-1B overexpressing cells and cells with knocked-down Gfi-1B were analyzed by oligonucleotide microarray technology and based upon rigorous statistical analysis of the data; relevant genes were chosen for confirmation by reserve transcriptase-polymerase chain reaction, including MYC/MYCBP and CDKN1A. Interestingly, transcripts within components of the signalling cascade of immune cells (PLD1, LAMP1, HSP90, IL6ST), of the tyrosine kinase pathway (TPR, RAC3) and of the transcription factors (RAC3, CEP290, JEM-1, ATR, MYC, SMC3, RARA, RBBP6) were found to be differentially expressed in Gfi-1B overexpressing cells compared to controls. Individual genes such as ZDHHC17, DMXL1, ZNF292 were found to be upregulated in Gfi-1B overexpressing cells. In addition, down-regulated transcripts showed cell signaling transcripts for several chemokine gene members including GNAL, CXCL5, GNL3L, GPR65, TMEM30, BCL11B and transcription factors (GTF2H3, ATXN3). In conclusion, several essential cell signalling factors, as well as transcriptional and post-translational regulation genes were differentially expressed in cells that overexpressed Gfi-1B compared to control cells with knocked-down Gfi-1B. Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations.
International Journal of Hematology 02/2008; 87(1):39-47. · 1.27 Impact Factor
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ABSTRACT: Here we report on the use of a new real-time polymerase chain reaction (PCR) method to detect and quantify the activating gene mutation of the tyrosine kinase JAK2. We evaluated patients with myelofibrosis with myeloid metaplasia (MMM; n=25) for the gene mutation prior to allogeneic stem cell transplantation and monitored them in the long-term follow up of 125 months (median 15, range 4-125) after transplant. The results obtained were correlated to the chimerism status of these patients. The JAK2 gene mutation was detected in 15 of 25 analyzed patients prior to transplant. Three patients who were again positive for JAK2 after transplant also had mixed chimerism status. These three patients relapsed from MMM shortly after JAK2 gene mutation was detected for the first time after transplant. Our presented data shows the feasibility of the detection of JAK2 gene mutation by real-time PCR as a minimal residual disease marker after transplant.
Transplantation 07/2007; 83(11):1518-20. · 4.00 Impact Factor
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ABSTRACT: Bronchiolitis obliterans (BO) and bronchiolitis obliterans organizing pneumonia (BOOP) are late-onset non-infectious pulmonary complications (LONIPCs) following allogeneic hematopoietic stem cell transplantation (HSCT). In the present study 10 of 197 conventionally prepared stem cell recipients developed BOOP after 365 days and 6 patients developed BO 333 days post-transplant. No BOOP or BO was diagnosed following T-cell depletion (p<0.05). Chronic GVHD was ascertained in all BOOP patients and appeared significantly (p<0,001) more frequent in the conventional transplant group. The data confirm a strong association between T-cell activity, chronic GVHD, BO and BOOP and point out the impact of T lymphocytes in the pathomechanism of BOOP.
Haematologica 04/2007; 92(4):558-61. · 6.42 Impact Factor
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Ahmet H Elmaagacli
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ABSTRACT: Monitoring of minimal residual disease (MRD) in patients with acute or chronic myeloid disorders is routinely performed after allogeneic or autologous transplantation. The detection of MRD helps to identify patients who are at high risk for leukemic relapse after transplantation. The most commonly used techniques for MRD detection are qualitative and quantitative PCR methods, fluorescence in situ hybridization (FISH), fluorescence-activated cell sorting (FACS), and cytogenetic analysis, which are often performed complementary in order to assess more precisely MRD. Here, we describe the most used sensitive real-time reverse-transcription (RT)-PCR methods for chronic and acute myeloid disorders. Besides protocols for real-time RT-PCR and multiplex RT-PCR procedures for the most common fusion-gene transcripts in acute and chronic myeloid disorders, methods for detection of disease-specific genetic mutated alterations as FLT3 gene-length mutations, and aberrantly expressed genes as WT1 gene transcripts, are described in detail for daily use.
Methods in molecular medicine 02/2007; 134:161-78.
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Biology of Blood and Marrow Transplantation 01/2007; 12(12):1350-1. · 3.87 Impact Factor
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ABSTRACT: Growth factor-independent 1B (GFI1B) is a transcription factor essential for the development and differentiation of erythroid and megakaryocytic lineages. We evaluated the GFI1B expression in erythroleukaemia and megakaryocytic leukaemia, as well as in patients with other subtypes of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), myelodysplastic syndrome (MDS), severe aplastic anaemia (SAA), myelofibrosis with myeloid metaplasia (MMM) and in healthy volunteers. GFI1B expression was increased at least threefold in patients with erythroleukaemia (P < 0.01 compared with controls) and megakaryocytic leukaemia (P < 0.05) as well as in their corresponding leukaemic cell lines HEL, K562, CMK and M-07e. Patients with undifferentiated or monocytic AML, ALL, MMM, MDS and CML had no significantly altered GFI1B expression, whereas GFI1B expression was decreased 10-fold in patients with SAA (P < 0.0001 compared with controls). Silencing GFI1B by transfection with small interfering RNA (siRNA) markedly reduced the proliferation rate in the leukaemic cell lines HEL, K562 and NB4 (P < 0.01). Concomitantly, we observed a two- to threefold increase in the apoptosis rate in these cells after transfection with siRNA towards GFI1B. Our data indicate that GFI1B plays a major role in AML-M6 and AML-M7 and qualifies as a target for anti-leukaemic strategies in these malignancies.
British Journal of Haematology 01/2007; 136(2):212-9. · 4.94 Impact Factor
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ABSTRACT: In the hematopoietic stem cell transplantation setting, granulocyte colony-stimulating factor (G-CSF) administration can reduce donor cell reactivity in vitro, but the clinical significance of this phenomenon was only sparsely defined.
We performed lymphocyte transformation tests in 28 related stem cell donors pre and 5 days post G-CSF treatment, respectively, and correlated proliferative responses of donor peripheral blood mononuclear cells with clinical parameters in the corresponding recipients.
In vitro reactions towards 4 mitogens and 12 recall antigens at day 5 post G-CSF administration were predictive for the occurrence of chronic graft-vs-host disease (cGVHD). Here, proliferative responses towards the mitogen anti-CD3 monoclonal antibody (OKT3) above median were most informative; this threshold could be determined by discrimination and receiver operating curve (ROC) analyses. In the whole cohort (18 human leukocyte antigen [HLA]-identical and 10 partially mismatched donor-recipient pairs), OKT3 responses predicted cGVHD with an odds ratio of 33.0, a sensitivity of 79%, and a specificity of 90%. A subgroup analysis of HLA-identical pairs even yielded an odds ratio of 85.0. Furthermore, bivariate analysis defined HLA compatibility and responses towards OKT3 as independent risk factors for cGVHD (p = 0.02 and p = 0.0007, respectively).
The proliferative capacity of G-CSF-mobilized donor cells appears as a graft factor that determines the future incidence of cGVHD in the corresponding recipient.
Experimental Hematology 01/2007; 34(12):1753-8. · 2.90 Impact Factor
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ABSTRACT: We compared the results of chimerism analyses with real-time SNP-PCR to those obtained by the classical STR-PCR method in 135 hematopoietic stem cell transplantation recipients. Using 10 different SNP gene loci, the SNP-PCR method was able to discriminate patient from donor cells in 125 of 135 cases (93%), whereas the use of 11 different STR gene loci with the STR-PCR analysis using agarose or polyacrylamide gel resolution resulted in accurate donor-host discrimination in all patients. Of the 470 analyzed samples we found in 74% concordant results for both chimerism methods. In all 26% discordant cases the SNP-chimerism method showed mixed chimerism (MC), whereas the STR-method found complete chimerism (CC). As a consequence, the SNP-PCR chimerism analysis method detected a MC prior to the occurrence of relapse significantly earlier than the STR-PCR chimerism method (120 vs. 30 days, P < 0.007). The probability of relapses was significantly higher in patients with increasing MC (70%) compared to 30% in patients with CC (P < 0.00001) associated with a significantly shorter overall survival in patients with increasing MC. The multivariate Cox model showed that chimerism analsis with SNP-PCR was the only significant risk factor predicting relapse (RR 6.08, P < 0.0001).Furthermore, we analyzed the chimerism status in male recipients with a female donor in 580 samples of 134 patients using quantitative real-time PCR of Y-chromosome-specific sequences and compared the results with interphase XY-fluorescent in situ hybridization (FISH). MC without signs of relapse was detected in 35% of samples using quantitative real-time PCR of Y-chromosome-specific sequences. The detected Y-DNA amounts were low compared to the amounts detected in 104 samples of 42 patients with leukemic relapse at the time of analysis (P < 0.0001). Quantitative real-time PCR of Y-chromosome-specific sequences detected therefore an increasing MC with high residual host DNA amounts approximately 143 days (mean) prior to the occurrence of relapse. By comparing the results of Y-chromosome PCR with the XY-FISH analysis we found concordant results in 73% in patients with myeloablative regimens. The XY-FISH could detect 12 relapses, whereas the Y-chromosome PCR detect 36 relapses by MC (P < 0.005). Residual host cells gradually decreased during the posttransplant period from a mean of 5.4 ng (first months) to 0.5 ng (above 5 years) without evidence of relapses. The probability of relapses was significantly higher in patients with increasing MC (100%) compared to 8% in patients with CC (P < 0.00001) associated with a significantly shorter overall survival in patients with increasing MC. The multivariate Cox model showed that chimerism analysis of Y-chromosome-specific sequences is an important risk factor for relapse (RR 17.0, P < 0.0001). We conclude that the use of real-time SNP or Y-PCR may be superior to the STR-PCR or interphase XY-FISH methods in detecting patients who are at high risk for relapse after transplant.
American Journal of Hematology 10/2006; 81(10):735-46. · 4.67 Impact Factor
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Ahmet H Elmaagacli,
Michael Koldehoff,
Heidrun Hindahl,
Nina K Steckel,
Rudolf Trenschel,
Rudolf Peceny,
Hellmut Ottinger,
Peter-Michael Rath,
Rudolf Stefan Ross,
Michael Roggendorf,
Hans Grosse-Wilde,
Dietrich W Beelen
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ABSTRACT: NOD2 and TLR-4 genes belong to the innate immune system that detects invading pathogens through several pattern-recognition receptors. Here we analyzed 403 patients for NOD2 gene mutations and 307 patients for TLR-4 gene mutations (Thr399Ile) with their respective donors and correlated the results with the incidence of acute graft-versus-host disease (aGVHD), severe acute GVHD (saGVHD), the risk for transplant-related mortality (TRM), overall survival (OS) and incidence of infectious complications.
We performed a retrospective single-center study. Genotyping of TLR-4 and NOD2 were evaluated by real-time polymerase chain reaction.
Surprisingly, we found a significant reduced incidence of aGVHD, saGVHD, and intestinal GVHD for patients with NOD2 gene mutations on the donor side with 50%, 0% and 2% compared to patients with the wild-type NOD2 gene with 65%, 17%, and 26%, respectively (P<0.02). However, the incidence of saGVHD increased in patients with NOD2 mutations on the patient and donor (P/D) side with 44% versus 17% compared to patients with the wild-type gene (P<0.03). TLR-4 gene mutations at P/D side had an increased risk for saGVHD with 42% versus 15% of patients with wild-type gene (P<0.04). OS, TRM, and incidence of infectious complications were not influenced by the mutated genes. Multivariate analysis confirmed that NOD2 gene mutations on the donor side had a reduced risk for saGVHD (P<0.001), whereas mutations of the NOD2 gene on P/D side had an increased risk for saGVHD (P<0.01) in our analysis.
These results suggest that NOD2 mutations have influence on the occurrence of acute GVHD after transplantation.
Transplantation 01/2006; 81(2):247-54. · 4.00 Impact Factor
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ABSTRACT: To examine how killer-cell immunoglobulin-like receptor (KIR) ligand incompatibilities effect molecular relapse (MR), we compared the occurrence of bcr-abl-positive reverse-transcriptase polymerase chain reaction (RT-PCR) results in 236 CML patients (pts) after human leukocyte antigen (HLA)-identical (n=158) (group 1), HLA class I antigen mismatched and KIR-ligand compatible (n=49) (group 2), and HLA class I antigen mismatched and KIR-ligand incompatible (n=29) (group 3) hematopoietic stem-cell transplantation.
We performed a retrospective single-center study. MR was evaluated using the real-time RT-PCR method for the detection of bcr-abl transcripts.
In the first group, 133 of 158 (84%) pts were in the first chronic phase of CML, and the corresponding figures were 33 of 49 (67%) pts in group 2 and 19 of 29 (64%) in group 3 (P<0.05). MR occurred in 1 of 29 (3%) pts in group 3 compared with 62 of 158 (39%) pts in group 1 and in 11 of 49 (22%) pts in group 2 (P<0.001). A hematologic relapse developed in 20 of 158 (13%) pts in group 1, 2 of 49 (4%) pts in group 2, and in 0 of 29 (0%) pts in group 3 (P<0.05). Multivariate analysis confirmed that KIR mismatches are a strong independent predictor for the occurrence of MR after transplantation (P<0.02). The 5-year overall survival rate did not vary greatly between the three groups (67% in group 1, 52% in group 2, and 66% in group 3).
These results suggest that KIR-ligand incompatibility is an important prognostic factor in the occurrence of MR after transplantation for CML.
Transplantation 07/2005; 79(12):1741-7. · 4.00 Impact Factor
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ABSTRACT: The Wilms' tumor gene (WT1) is aberrantly over-expressed in leukemic cells. Therefore, we wanted to study the effect of small interfering (siRNA) targeting WT1 in leukemic cells and normal CD34-positive cells with regard to proliferation, induction of apoptosis, and cell differentiation. Furthermore, we wanted to evaluate whether the additional use of BCR-ABL siRNA could increase the anti-leukemic effects of WT1 siRNA in chronic myeloid leukemia (CML) cells.
We measured WT1 expression by reverse transcription polymerase chain reaction (RT-PCR) in various cell lines and in leukemic cells from patients, then transfected the cells with WT1-specific and BCR-ABL-specific siRNA before carrying out microarray analysis. We used the tunnel assay to measure apoptotic cells.
We observed a reduction of WT1 gene expression, measured by real-time RT-PCR, in all studied cell lines: K-562, Kasumi-1, MV 4-11 and NB-4, as well as in cells of AML and CML patients. The results also demonstrated that WT1 siRNA significantly induced apoptosis and inhibited proliferation in MV4-11 cells, NB-4 cells, Kasumi-1 cells (p<0.01) and in K-562 cells (p<0.02) versus controls. In normal CD34-positive cells, the proliferation was only slightly inhibited (by about 20%) and no induction of apoptosis was found. Combined transfection with WT1 and BCR-ABL siRNA together in K-562 cells increased the inhibition of the rate of proliferation and the rate of induced apoptosis compared to transfection with BCR-ABL siRNA or WT1 siRNA alone (p<0.01). We found that most genes involved in cell signaling and protein metabolism were regulated by the WT1 gene in K-562 cells in a microarray analysis.
In conclusion, WT1 might be a suitable target for new therapeutic strategies using siRNAs in leukemic cells.
Haematologica 04/2005; 90(3):326-34. · 6.42 Impact Factor
