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Hematology Reports
Volume 4
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Hematology Reports is published by MDPI from Volume 14 Issue 1 (2022). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with PAGEPress.

Hematol. Rep., Volume 4, Issue 3 (July 2012) – 6 articles

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4 pages, 623 KiB  
Article
Overexpression of Lung Resistance-Related Protein and P-Glycoprotein and Response to Induction Chemotherapy in Acute Myelogenous Leukemia
by Kazue Tsuji, Yan-Hua Wang, Minoko Takanashi, Tsuyoshi Odajima, Gabriel A. Lee, Hiroki Sugimori and Toshiko Motoji
Hematol. Rep. 2012, 4(3), e18; https://doi.org/10.4081/hr.2012.e18 - 01 Oct 2012
Cited by 13
Abstract
Lung resistance-related protein (LRP) and P-glycoprotein (P-gp) are associated with multidrug resistance. P-gp overexpression reduces intracellular anticancer drug concentrations and is correlated with low remission rates. However, whether the presence of LRP influences the response to induction chemotherapy remains controversial. Therefore, we investigated [...] Read more.
Lung resistance-related protein (LRP) and P-glycoprotein (P-gp) are associated with multidrug resistance. P-gp overexpression reduces intracellular anticancer drug concentrations and is correlated with low remission rates. However, whether the presence of LRP influences the response to induction chemotherapy remains controversial. Therefore, we investigated the relationship of LRP and P-gp overexpression with the response to induction chemotherapy. Univariate analysis revealed that there was a significant difference between complete remission rates for acute myelogenous leukemia patients depending on their blast cell expressions, between LRP positive versus negative, P-gp positive versus negative, and LRP/P-gp double positive versus other groups. Crude odds ratios (ORs) for complete remission were 0.390, 0.360, and 0.307 for LRP positive, for P-gp positive, and LRP/P- gp double positive patients, respectively. After controlling the confounding variables by stepwise multivariate logistical regression analysis, the presence of LRP/P-gp double positivity and P-gp positivity were found to be independent prognostic factors; adjusted ORs were 0.233 and 0.393, respectively. Furthermore, the monoclonal antibody against LRP significantly increased daunorubicin acumulation (P = 0.004) in the nuclei of leukemic blast cells with LRP positivity in more than 10% of the cells. An LRP reversing agent, PAK-104P, was found to increase the daunorubicin content with marginal significance (P = 0.060). The present results suggest that not only the presence of P-gp, but also LRP in leukemic blast cells is a risk factor for resistance to induction chemotherapy. Inhibiting LRP function, similar to the inhibition of P-gp function, will be necessary to improve the effectiveness of induction chemotherapy. Full article
6 pages, 772 KiB  
Article
Translocation t(11;14) (q13;q32) and Genomic Imbalances in Multi-Ethnic Multiple Myeloma Patients: A Malaysian Study
by Ivyna Bong Pau Ni, Ng Ching Ching, Chang Kian Meng and Zubaidah Zakaria
Hematol. Rep. 2012, 4(3), e19; https://doi.org/10.4081/hr.2012.e19 - 28 Sep 2012
Cited by 9
Abstract
More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR)-based translocation detection assay to detect BCL1/JH t(11;14) (q13;q32) in [...] Read more.
More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR)-based translocation detection assay to detect BCL1/JH t(11;14) (q13;q32) in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH) analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14) (q13;q32) translocation (n = 15 of 105). We found no significant correlation between this translocation with age (P = 0.420), gender (P = 0.317), ethnicity (P = 0.066) or new/relapsed status of multiple myeloma (P = 0.412) at 95% confidence interval level by Χ2 test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14)(q13;q32) translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14) (q13;q32) translocation. Full article
3 pages, 624 KiB  
Case Report
Pure Red Cell Aplasia in a Simultaneous Pancreas-Kidney Transplantation Patient: Inside the Erythroblast
by Francesca Labbadia, Eduardo Salido-Fierréz, Juliana Majado-Martinez, Valentin Cabañas-Perianes and José M. Moraleda Jiménez
Hematol. Rep. 2012, 4(3), e17; https://doi.org/10.4081/hr.2012.e17 - 10 Sep 2012
Cited by 3
Abstract
A case of pure red cell aplasia in a simultaneous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unresponsive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of parvovirus pure red cell aplasia, which was confirmed [...] Read more.
A case of pure red cell aplasia in a simultaneous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unresponsive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of parvovirus pure red cell aplasia, which was confirmed with serology and polymerase chain reaction positive for parvovirus B19 DNA in peripheral blood. After the administration of intravenous immunoglobulin the anemia improved with a rising number of the reticulocytes. Full article
5 pages, 799 KiB  
Case Report
B-Cell Acute Lymphoblastic Leukemia with t(4;11)(q21;q23) in a Young Woman: Evolution into Mixed Phenotype Acute Leukemia with Additional Chromosomal Aberrations in the Course of Therapy
by Giovanni Carulli, Alessandra Marini, Maria I. Ferreri, Antonio Azzarà, Virginia Ottaviano, Tiziana Lari, Melania Rocco, Stefano Giuntini and Mario Petrini
Hematol. Rep. 2012, 4(3), e15; https://doi.org/10.4081/hr.2012.e15 - 06 Sep 2012
Cited by 8
Abstract
About 5% of adult B-cell acute lymphoblastic leukemias (B-ALL) are characterized by t(4;11)(q21;q23), which confers peculiar features to this B-ALL subtype, including a very immature immunophenotype and poor prognosis. We describe the case of a 21-year-old female who presented with B-ALL carrying the [...] Read more.
About 5% of adult B-cell acute lymphoblastic leukemias (B-ALL) are characterized by t(4;11)(q21;q23), which confers peculiar features to this B-ALL subtype, including a very immature immunophenotype and poor prognosis. We describe the case of a 21-year-old female who presented with B-ALL carrying the t(4;11)(q21;q23) and blasts positive for CD19, TdT, CD79a, CD38, HLA-DR. Before completing the Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) therapy regimen, the B-cell leukemic clone still was detected, but an additional leukemic clone appeared, with morphology and immunophenotype (CD13, CD33, CD64, CD38, CD56, CD15, CD4dim) compatible with derivation from the myeloid/monocytic lineage. Karyotype showed the co-existence of three cell lines, with persistence of t(4;11)(q21;q23) and appearance of +8,+12,+13 and two der(4). The patient died because of disseminated intravas- cular coagulation. Our report describes a rare, possible evolution of such a subtype of B-ALL, with transformation into mixed phenotype acute leukemia in the course of therapy. This finding suggests a blast cell derivation from a common lymphoid/monocytic precursor leading to a final bilineal acute leukemia. Full article
4 pages, 656 KiB  
Case Report
Epstein-Barr Virus-Negative Aggressive Natural Killer-Cell Leukaemia with High P-Glycoprotein Activity and Phosphorylated Extracellular Signal-Regulated Protein Kinases 1 and 2
by Sanja Perkovic, Sandra Basic-Kinda, Vladimir Gasparovic, Zeljko Krznaric, Jaksa Babel, Ivana Ilic, Igor Aurer and Drago Batinic
Hematol. Rep. 2012, 4(3), e16; https://doi.org/10.4081/hr.2012.e16 - 04 Sep 2012
Cited by 5
Abstract
Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with [...] Read more.
Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56+ NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy. Full article
5 pages, 354 KiB  
Article
Combination of Cyclophosphamide, Etoposide, Carboplatin and Dexamethasone as a Salvage Regimen for Refractory Multiple Myeloma Patients: A Comparison with a Historical Control Group
by Reza Safaee, Ahmad Ahmadzadeh, Ramezanali Sharifian, Amirhossein Emami, Mir Saeed Yekaninejad, Mohammad Hossein Jalili and Armita Valizadeh
Hematol. Rep. 2012, 4(3), e14; https://doi.org/10.4081/hr.2012.e14 - 11 Jul 2012
Cited by 2
Abstract
The aim of this study was to design a regimen for refractory multiple myeloma with minimum complications to achieve a reasonable response. Fifteen patients with active multiple myeloma after at least two lines of conventional treatment underwent therapy with our regimen for two [...] Read more.
The aim of this study was to design a regimen for refractory multiple myeloma with minimum complications to achieve a reasonable response. Fifteen patients with active multiple myeloma after at least two lines of conventional treatment underwent therapy with our regimen for two cycles. Disease activity was evaluated after the last cycle. Another 15 patients with refractory multiple myelomas that had previously received only supportive therapy and pain management formed a historical control group. The follow-up period was 12 months for each study group. Of the patients receiving therapy, 6.7% achieved a complete response and 26.7% a partial response; overall response rate was 33.3%. Stable disease was achieved in 46.7% and 20% of the patients had progressive disease. There was no treatment related mortality. The hazard rate of death was 0.73 lower in the intervention group than in the historical control group. In the historical control group, 60% had progressive disease and 40% had stable disease; approximately 40% of patients died during the 12-month follow up. Also, the severity of pain was significantly reduced in the intervention group (P = 0.033). Our chemotherapy regimen showed a reasonable response in end stage patients with multiple myeloma in terms of disease control, reducing bone pain and improving survival, in addition to reducing toxicity. Full article
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