GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Leukemia Research Reports, Elsevier BV, Vol. 2, No. 2 ( 2013), p. 51-53
    Type of Medium: Online Resource
    ISSN: 2213-0489
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 2706248-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2012
    In:  Leukemia Research Vol. 36, No. 4 ( 2012-4), p. 392-393
    In: Leukemia Research, Elsevier BV, Vol. 36, No. 4 ( 2012-4), p. 392-393
    Type of Medium: Online Resource
    ISSN: 0145-2126
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2012
    detail.hit.zdb_id: 2008028-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Experimental Hematology, Elsevier BV, Vol. 39, No. 11 ( 2011-11), p. 1081-1089
    Type of Medium: Online Resource
    ISSN: 0301-472X
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2005403-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: British Journal of Haematology, Wiley, Vol. 162, No. 1 ( 2013-07), p. 141-144
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 1475751-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4007-4007
    Abstract: Abstract 4007 Background: An increasing body of evidence in different organ systems suggests that the presence of the cytosolic enzyme Aldehyde Dehydrogenase (ALDH) correlates to stemcellness. Thus, in mobilized peripheral blood stem cells (PBSCs), the side scatter low ALDH bright (SSCloALDHbr) population seems to be highly enriched for HSC as determined e.g. by Fallon et al1. However, these interesting preliminary findings need confirmation. Problem formulation: The generally accepted indirect relationship between CD34 content on the one hand, and successful hematopoietic regeneration after transplant on the other, is at least to a certain extent marred by the observation that, despite receiving sufficient weight-correlated amounts of CD34 positive HSC, some patients experience prolonged time to regeneration. Hypothesis: We hypothesized that the number of CD34+SSCloALDHbr is predictive of time to short and long-term regeneration following autologous bone marrow transplantation compared to the number of CD34+ cells alone. Results: PBSCs from 30 patients with refractory or relapsed diffuse large cell B-lymphoma referred for autologous stem cell transplantation after having failed at least three cytoreductive regimens were analyzed for ALDH expression. Laboratory results were registered on day 14 and day 100 post transplantation. Time to absolute neutrophil count (ANC) above 0,5 × 106/mL on two consecutive days was registered for each of the 30 patients. While a trend was noted for number of reinfused viable CD34+ cells (106/kg) to be correlated to ANC 〉 0,5 × 106/mL r=0.33, P = 0.07), only the CD34+SSCloALDHbr population correlated significantly to time to ANC 〉 0,5 × 106/mL (r=0.41, P =0.024). Moreover, while a positive correlation was observed between both of the analyzed subpopulations and CFU-GM proliferation, this correlation was strongest for the number of reinfused CD34+SSCloALDHbr/kg (r= 0.84, P 〈 0.001). While neither of the analyzed subpopulations could be correlated to time to short term platelet recovery (defined as platelets 〉 20 × 106/mL on two consecutive days) an interesting finding emerged, when we considered day 100 platelet recoveries. Here, 11 patients were grouped as poor mobilizers (PM) having not attained a platelet count of 100 × 106/mL at day 100, and 16 patients were grouped as good mobilizers (GM) while in three cases no data were available. While mere CD34 enumeration was once more not informative, we observed a trend towards low numbers of CD34+SSCloALDHbrcells in the grafts in PM (p=0.06). With regard to long-term erythroid engraftment (defined as Hgb 〈 100 g/L at day 100) 6 were PM (21 GM and data missing in 3) a significantly lower fraction of reinfused CD34+SSCloALDHbrwere administered to PM compared to GM (p=0.01). Once more, no significant difference in number of infused viable CD34+ cells between the groups was observed. Conclusion: In the autologous transplant setting the addition of SSCloALDHbrto standard CD34 enumeration seems to constitute a valuable marker for the identification of both time to ANC 〉 0,5 × 106/mL and inferior day +100 hematopoietic regeneration. While the assay does entail extra lab efforts, this layout is probably amply repaid by the possibility to institute pre-emptive therapy in PM patients. Moreover, application of the assay at the onset of leukapheresis sessions could provide a window of opportunity to administer alternative mobilization regimens, i.e. containing Plerixafor. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3235-3235
    Abstract: Introduction Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal diseases marked by dysplasia in the bone marrow (BM) causing cytopenias in the peripheral blood and with an inherent tendency to progress to acute myeloid leukemia (AML). Myelodysplastic syndrome has generally been regarded a stem cell disease, which very recent research has emphasized to hold true also for low-risk MDS (Woll, P. S. et al Cancer Cell. 2014). In AML, we have identified the human Myeloid Inhibitory C-type lectin-like receptor (hMICL) (also named CLL-1 or CLEC12A) as a stable and reliable marker at diagnosis and as a tool for assessing minimal residual disease (Roug, A. S. et al Br. J. Haematol. 2014). Furthermore, hMICL has been proposed as a marker of the leukemic stem cell (LSC) since it is present on CD34+CD38- cells in the majority of CD34-positive AMLs, while it is absent on the CD34+CD38- cell compartment in normal controls (van Rhenen, A. et al Leukemia. 2007). Previous studies have shown aberrant marker-expression on CD34+CD38- cells in MDS, e.g. CD7 or CD2, but only in minor fractions of patients (Xie, W. et al. Cytometry A. 2010). Using multicolor flowcytometry, we have examined the aberrant expression of hMICL on the CD34+CD38- stem cell compartment from 19 untreated MDS patients. We correlated the aberrant hMICL positive cells as a percentage of the total CD34+CD38- compartment (CD34+CD38-hMICL+/CD34+CD38-) to follow-up data. Materials and methods Bone marrow (BM) samples were obtained from 19 MDS patients diagnosed and followed at the Department of Hematology, Aarhus University Hospital from January 2010 to January 2011. Diagnosis was determined by morphology according to the 2008 WHO classification. Risk stratification of patients was done using the International Prognostic Scoring System (IPSS). All samples were collected before treatment with a cytoreductive agent or 5-azacytidine. Normal bone marrow (NBM) from 11 healthy volunteers served as controls. Following lysis of red blood cells, BM was stained with the following monoclonal antibodies: anti-CD34 APC, anti-CD38 FITC, anti-CD45 PerCP-Cy5.5 and anti-hMICL PE. Data acquisition was performed on a FACSCanto II and subsequently analyzed using FACSDiva Software. Using the back-gating strategy, the CD34+CD38-hMICL+ cell subset was shown to cluster together in an FSC-SCC plot. A total number of 5 clustered events were considered significant for further analyses. Results and perspectives The median age at sampling was 69 years (range 44-83 years). According to IPSS, 1 patient was classified as low-risk, 11 patients as intermediate-1 and 3 patients as intermediate-2. Four patients could not be classified. Consistent with previous reports, hMICL was not found on CD34+CD38- cells in any of the 11 NBM examined (0.0%) whereas aberrant hMICL expression was present on the CD34+CD38- stem cells in 16/19 (84%) of MDS cases. In MDS, the CD34+CD38-hMICL+ cells amounted a median of 5.68% (range 0,0-56.94%) of the CD34+CD38- subset, which was significantly different from NMB (p 〈 0.0001) (Figure 1A). The median follow-up period for the cohort was 3.7 years. Patients with fractions of hMICL positive CD34+CD38- cells above the median (5.68%) showed a significantly shorter progression free survival (PFS) compared to patients with hMICL+ fractions below the median (p=0.01) (Figure 1B). The same trend was evident with regards to overall survival (OS), although borderline significant (p=0.06) (Figure 1C). The aberrant expression of hMICL on CD34+CD38- stem cells from MDS patients belonging to both low- and intermediate risk groups identifies hMICL as a potential LSC-marker in this heterogeneous group of diseases. A considerable advantage of hMICL is its complete absence on normal hematopoietic stem cells and the fact that it was present in the majority of MDS cases studied. Despite the small patient-number in our cohort, the impact of a high hMICL+ stem cell fraction on PFS and OS is evident. Thus, hMICL marking of the CD34+CD38- stem cell compartment might serve as a prognostic indicator in the future. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    Online Resource
    Online Resource
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 5643-5643
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5643-5643
    Abstract: Markers indicative of prognosis play a consequential role in the clinical management of patients suffering from chronic B-cell lymphocytic leukemia (B-CLL). Soluble CD163 (sCD163) has been shown to be a useful biomarker in a wide variety of disease entities (Moller, 2012), however its presence in B-CLL has not been addressed. Using an enzyme-linked immunosorbent assay the concentration of sCD163 was measured in peripheral blood of 30 B-CLL patients at diagnosis. The results were related to the course of disease for up to two years post diagnosis. The median level of sCD163 in the plasma was not significantly higher in the B-CLL patients (2.085 mg/L, range 0.77- 9.01 mg/L) than in an age-matched control group (1.800 mg/L, range 0.97-2.45 mg/L) (n=10) (p=0.157). As CD163 is a monocyte/macrophage specific membrane protein, the relationship between the percentage of monocytes and the level of sCD163 was relevant. The level of sCD163 did not correlate with the percentage of monocytes in peripheral blood of the patients, but as previously described, there was an inverse correlation between measured sCD163 and the CD163 surface expression as measured by mean fluorescence intensity on the monocytes (r=0.088, p= 0.658 and r= -0.476, p=0.01, respectively) (Davis et al. 2005). Elevated levels of sCD163 have been linked to bacterial infection however in neither the B-CLL cohort nor the healthy control group, a correlation was found between the levels of sCD163 and CRP concentrations (r=0.24 and p=0.23 in B-CLL, and r=0.10 and p=0.81 in healthy controls) (Knudsen et al., 2007). To test the prognostic impact of sCD163 the B-CLL patients were divided into two subsets using the highest level of sCD163 measured in the age-matched healthy control group as a cut-off. Hence, 11 of 30 B-CLL patients were assigned to an sCD163high group. In total, 7/30 (23%) patients experienced disease progression defined as need for cytoreductive treatment within the two years follow-up period. In more detail, 5/11 sCD163high patients (45%) and 2/19 patients (11%) in the sCD163low group received therapy (p=0.068). When analyzing the relevance of sCD163 in terms of predicting disease progression, there was a significant difference between patients in the two groups, indicating that patients with high concentrations of sCD163 in the plasma progressed more rapidly (p=0.029) (Figure 1A). In this cohort, CD38 expression was also of prognostic value for progressive disease (p=0.006) (Figure 1B), while b2M was of borderline significance (p=0.051) (Figure 1C). The role of mutational status as predictor of short time to treatment was not significant (p=0.21) (Figure 1D). When performing the log-rank univariate analyses on the dataset, there was an obvious increased hazard of receiving treatment for patients in the sCD163high group compared to the sCD163low patients (Table I). As expected, CD38 expression, b2M, and IgVH mutational status were albeit to varying degrees covariates in the time to treatment analyses (Table I). The data strongly indicate that sCD163 is a prognostic marker in B-CLL. The study is limited by the cohort size, however, indubitably, the results lay the ground for a larger study. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    Online Resource
    Online Resource
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 2626-2626
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2626-2626
    Abstract: Flow cytometry constitutes a cornerstone in the diagnosis and follow up of acute myeloid leukemia (AML) and it is based on the identification of leukemia-associated immunophenotypes (LAIPs). We have recently demonstrated that the C-type lectin hMICL in combination with CD123 constitute a highly stable and reliable LAIP marker combination at diagnosis and relapse. In addition, we have shown that an hMICL/CD123-based assay is an effective tool for the monitoration of minimal residual disease (MRD) in AML. To what extent hMICL/CD123 marking identifies early leukemic cells is, however, not established. We hypothesized that this could be addressed by studying molecular aberrations in leukemic cell subsets according to their expression of hMICL and CD123. Employing cell sorting and mutational analyses, we here establish the leukemic origin of hMICL and CD123 expressing cell populations. Analyzing diagnostic AML samples with homozygous FLT3-ITD aberrations allowed for verification of pure malignant clones. Five patients with FLT3-ITD allelic burden of 〉 50% (range 77-93%, median 85%) as measured by DNA fragment analysis by capillary electrophoresis on mononuclear cells (MNC) were identified in our local database of 600 cases. We found that 5/5 patients displayed a normal karyotype and carried NPM1 mutations (NPM1 allelic burden 42-48%, median 46%). In contrast, mutations in FLT3-D835, IDH1-R132, c-KIT-D816V or indel mutations in CEBPA and WT-1 exon 7 were absent. From samples of cryopreserved mononuclear cells (bone marrow (n=4) and peripheral blood (n=1)), CD45low/SSClow blast cell subsets with the following immunophenotypes were sorted by FACS: CD34+/hMICL+/CD123+, CD34+/hMICL+/CD123-, CD34+/hMICL-/CD123+, and CD34+/hMICL-/CD123-. In one case of CD34 negative AML the sorted subsets were CD34-/hMICL+/CD123+, CD34-/hMICL+/CD123-, CD34-/hMICL-/CD123+, and CD34-/hMICL-/CD123-. Sorted cell subsets were analyzed for FLT3-ITD and NPM1 mutations using fragment analysis by capillary electrophoresis. The results of the fragment analyses are tabulated in the table below. In all cases the hMICL and CD123 expressing subsets of interest closely approximated 100% FLT3-ITD allelic burden. In contrast, hMICL-/CD123- cells approximated only a 50% FLT3-ITD allelic burden. Of note, an extended search in our AML database, revealed only 9 of 600 patients to have an FLT3-ITD allelic burden 〉 50% (range 52-94%, median 81%) hence indicating a state of either homo- or hemizygosity. Interestingly, with the exception of one case carrying a chromosome 13 duplication, each of these 9 patients also harbored a mutation in the NPM1 gene as the only other known aberration. In conclusion using AML patients with high FLT3-ITD allelic burdens we have been able to show that blasts expressing hMICL and/or CD123 at diagnosis are indeed malignant thus further substantiating the use of these antigens in AML MRD detection. Additionally, a direct relationship between NPM1 and FLT3-ITD homo-/hemizygosity may be suggested in the evolution of the malignant clone.Phenotype of sorted cell subsetNumber of patientsFLT3-ITD allelic burden (%) Min-max (median)NPM1 allelic burden (%) Min-max (median)MNC577-93 (85)42-48 (46)CD45low/SSClow/CD34+/hMICL+/CD123+495-100 (98)48-50 (49)CD45low/SSClow/CD34+/hMICL+/CD123-1*9248CD45low/SSClow/CD34+/hMICL-/CD123+497-100 (99)47-51 (48.5)CD45low/SSClow/CD34+/hMICL-/CD123-436-68 (47)16-38 (25)CD45low/SSClow/CD34-/hMICL+/CD123+110046CD45low/SSClow/CD34-/hMICL+/CD123-19448CD45low/SSClow/CD34-/hMICL-/CD123+110047CD45low/SSClow/CD34-/hMICL-/CD123-17735*Subset only present in one of four patients Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    In: Leukemia Research Reports, Elsevier BV, Vol. 3, No. 2 ( 2014), p. 94-97
    Type of Medium: Online Resource
    ISSN: 2213-0489
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 2706248-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: Cytotherapy, Elsevier BV, Vol. 16, No. 3 ( 2014-03), p. 392-401
    Type of Medium: Online Resource
    ISSN: 1465-3249
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 2071176-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...