Home About us Contact
|
Home About us Contact | ||
|
|
||
Acute Myeloblastic Leukemia (acute + myeloblastic_leukemia)
Selected AbstractsIncreased immature hematopoietic progenitor cells CD34+/CD38dim in myelodysplasiaCYTOMETRY, Issue 2 2006Mariela B. Monreal Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells. Methods We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS). Results Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P , 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03). Conclusion Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases. © 2006 International Society for Analytical Cytology [source] Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11)GENES, CHROMOSOMES AND CANCER, Issue 4 2003Toshihiko Imamura In this study, we examined a pediatric case of therapy-related myelodysplastic syndrome (tMDS). The symptoms developed 17 months after treatment for acute myeloblastic leukemia (AML, M2 subtype according to the French,American,British [FAB] classification) involving a chromosome abnormality at t(8;21)(q22;q22). Upon diagnosis of tMDS, spectral karyotyping analysis detected a new chromosomal translocation at t(2;8)(p23;p11.2). In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8. However, no partner gene on 2p23 could be identified. To our knowledge, this is the first report of tMDS associated with a rearrangement of the MOZ gene. MOZ-linked fusion proteins such as MOZ-CBP (CREB binding protein), MOZ-TIF2 (transcriptional intermediary factor 2), and MOZ-p300 (adenoviral E1A-associated protein) are associated with AML chromosomal abnormalities at t(8;16)(p11;p13), inv(8)(p11q13), and t(8;22)(p11;q13), respectively, and are thought to account for leukemogenesis occurring through the aberrant regulation of histone acetylation. Through a similar mechanism, we believe that MOZ, fused to an unidentified partner gene at 2p23, may have caused an alteration in histone acetylation, resulting in the development of tMDS in this patient. © 2003 Wiley-Liss, Inc. [source] Myeloprotective effect of short-course high-dose methylprednisolone treatment before consolidation therapy in children with acute myeloblastic leukemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2005Selin Aytaç Elmas Abstract In our previous studies, short-course high-dose methylprednisolone (HDMP) has been shown to shorten the chemotherapy-induced neutropenic period by stimulating the CD34+ hematopoietic progenitor cells in children with acute leukemia. In this study, we investigate the role of short-course HDMP on induction of a myeloprotective effect when administered before consolidation therapy consisting of high-dose cytosine arabinoside and daunorubicin. Thirty-four consecutive newly diagnosed children with acute myeloblastic leukemia (AML) who received 64 courses of consolidation regimen were entered into the study. The patients received HDMP (group A) at a daily dose of 30 mg/kg methylprednisolone starting 4 days before the initiation of consolidation therapy. The control group did not receive HDMP (group B). There were no differences in the white blood cell (WBC) and absolute neutrophil counts (ANC) between group A (at day ,4) and group B (at day 0) at the beginning of the study (medians: 3 × 109/L vs. 3.2 × 109/L and 1.5 × 109/L vs. 1.7 × 109/L, respectively). The WBC count increased significantly from 3 × 109/L to 6.4 × 109/L, and ANC increased from 1.5 × 109/L to 3.9 × 109/L after 4 days of HDMP treatment in group A (P < 0.01). Following high-dose chemotherapy, the median values of WBC and ANC also remained higher than the control values during the 16 days of the follow-up period. The neutropenic period was significantly shorter in the HDMP group than in the control group (9 ± 5.2 days vs. 22 ± 4.7 days) (P < 0.05). The duration of hospitalization and the interval between two chemotherapy cycles were significantly decreased in group A when compared group B (9 ± 2.7 vs. 14 ± 2.7 days; 22 ± 4.7 vs. 26 ± 4.2 days, respectively) (P < 0.05). Moreover, following consolidation therapy, the number of patients with ANC values below 0.5 × 109/L was lower in group A when compared the group B. In conclusion, the administration of short-course (4 days) HDMP before high-dose chemotherapy has been found to be beneficial for reducing the duration and severity of neutropenia. Further studies with short-course HDMP are required to evaluate its myeloprotective effects in patients with other malignancies. Am. J. Hematol. 80:1,5, 2005. © 2005 Wiley-Liss, Inc. [source] The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1, form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 3 2009Michael Frosch Objective Fever of unknown origin is a diagnostic challenge in children, especially for differentiation of systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) and infectious diseases. We undertook this study to analyze the relevance of myeloid-related proteins (MRPs) 8 and 14, endogenous activators of Toll-like receptor 4, in diagnosis and pathogenesis of systemic-onset JIA. Methods Serum concentrations of MRP-8/MRP-14 were analyzed in 60 patients with systemic-onset JIA, 85 patients with systemic infections, 40 patients with acute lymphoblastic leukemia, 5 patients with acute myeloblastic leukemia, 18 patients with neonatal-onset multisystem inflammatory disease (NOMID), and 50 healthy controls. In addition, we investigated the link between interleukin-1, (IL-1,) and MRP-8/MRP-14 in systemic-onset JIA. Results Serum MRP-8/MRP-14 concentrations were significantly (P < 0.001) elevated in patients with active systemic-onset JIA (mean ± 95% confidence interval 14,920 ± 4,030 ng/ml) compared with those in healthy controls (340 ± 70 ng/ml), patients with systemic infections (2,640 ± 720 ng/ml), patients with acute lymphoblastic leukemia (650 ± 280 ng/ml), patients with acute myeloblastic leukemia (840 ± 940 ng/ml), and patients with NOMID (2,830 ± 580 ng/ml). In contrast to C-reactive protein levels, MRP-8/MRP-14 concentrations distinguished systemic-onset JIA from infections, with a specificity of 95%. MRP-14 in serum of patients with systemic-onset JIA was a strong inducer of IL-1, expression in phagocytes. Conclusion The analysis of MRP-8/MRP-14 in serum is an excellent tool for the diagnosis of systemic-onset JIA, allowing early differentiation between patients with systemic-onset JIA and those with other inflammatory diseases. MRP-8/MRP-14 and IL-1, represent a novel positive feedback mechanism activating phagocytes via 2 major signaling pathways of innate immunity during the pathogenesis of systemic-onset JIA. [source] S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown originARTHRITIS & RHEUMATISM, Issue 12 2008Helmut Wittkowski Objective Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents. Methods Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme-linked immunosorbent assay. Results The mean ± 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 ± 2,690 ng/ml; in patients with FMF, 6,720 ± 4,960 ng/ml; in patients with NOMID, 720 ± 450 ng/ml; in patients with MWS, 150 ± 60 ng/ml; in patients with infections, 470 ± 160 ng/ml; in patients with ALL, 130 ± 80 ng/ml; in patients with AML, 45 ± 60 ng/ml; in healthy control subjects, 50 ± 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively. Conclusion S100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic-onset JIA or FMF, which may point to as-yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO. [source] Aetiology of childhood leukemiaBIOELECTROMAGNETICS, Issue S7 2005Tracy Lightfoot Abstract Leukemia is the most common cancer to affect children, accounting for approximately a third of all childhood cancers. The major morphological subtypes of leukemia, acute lymphoblastic leukemia (ALL), and acute myeloblastic leukemia (AML), are characterized by chromosomal translocations involving over 200 genes including mixed lineage leukemia (MLL), TEL, and AML1. Chromosomal translocations involving the MLL gene at 11q23 are a common feature of infant acute leukemia, found in up to 80% of all cases, and there is strong evidence that rearrangements involving the MLL gene or the TEL-AML1 gene fusion can originate in utero. As with most other cancers, the mechanism by which leukemia arises is likely to involve gene-environment interactions. Accordingly, it is important to identify exposures that cause DNA damage and induce chromosome breaks which are inadequately repaired, ultimately leading to the initiation and disease progression. Exposures acting before birth and early in life has long been thought to be important determinants of leukemia, and the list of suspected chemical, physical, and biological agents continues to increase. Unfortunately, the evidence regarding the majority of suggested exposures is limited and often contradictory, and there are areas, which clearly warrant further investigation in order to further our understanding of the aetiology of childhood leukemia. Bioelectromagnetics Supplement 7:S5,S11, 2005. © 2005 Wiley-Liss, Inc. [source] Reduced intensity conditioning prior to allogeneic stem cell transplantation for patients with acute myeloblastic leukemia as a first-line treatmentCANCER, Issue 9 2005Didier P. Blaise M.D. Abstract BACKGROUND Thirty-three patients (median age 52; range 26,60) with acute myeloblastic leukemia (AML) were included in a pilot study of allogeneic stem cell transplantation (Allo-SCT) following a reduced-intensity conditioning (RIC). METHODS Patients achieving first complete remission (CR1) were selected for their high-risk clinical and/or leukemic features. All patients received two courses of consolidation chemotherapy including one high-dose cytarabine course. Among them, 13 patients in addition received a high-dose melphalan course followed by autologous SCT. Then, all patients received an RIC Allo-SCT combining fludarabine, busulfan, and antithymocyte globulin. RESULTS All patients engrafted had cumulative incidences of Gluksberg System Grade 2 acute and chronic graft-versus-host-disease (GVHD) of 24 (9,39%) and 64 (48,80%), respectively. Three patients died from nonrelapse causes (NRD) (cumulative incidence: 9%, 95% confidence interval (CI): 0-19) and 6 relapsed (cumulative incidence: 18%, 95% CI: 5,31). With a median follow-up of 18 months (range 7,52) after Allo-SCT, 26 patients are alive, of whom 24 remained in CR1 for a 2-year overall survival and leukemia-free survival (LFS) probabilities of 79 (range 61,90%) and 76 (range 59,87%), respectively. In a ,landmark' analysis starting on Day 100, the occurrence of chronic GVHD was associated with a lower relapse rate (0% vs. 44%: P = 0.007) and improved outcome (LFS; 95% vs. 53%, P = 0.007; overall survival, 95% vs. 61%, P = 0.05). CONCLUSIONS We conclude that the sequential combination of intensive chemotherapy and allogeneic immunotherapy might offer relatively low NRD and leukemia relapse rates even in high-risk patients. Cancer 2005. © 2005 American Cancer Society. [source] | |||||||||||||