Switching drugs midstream for patients with chronic myeloid leukemia.

Posted by rob on August 20, 2015 under Uncategorized | Comments are off for this article

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Switching drugs midstream for patients with chronic myeloid leukemia.

Clin Adv Hematol Oncol. 2014 Jul;12(7):466-8

Authors: DeAngelo DJ

PMID: 25322328 [PubMed - indexed for MEDLINE]

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miRNAs as Biomarkers in Chronic Myelogenous Leukemia.

Posted by rob on August 19, 2015 under Uncategorized | Comments are off for this article

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miRNAs as Biomarkers in Chronic Myelogenous Leukemia.

Drug Dev Res. 2015 Aug 18;

Authors: Kotagama K, Chang Y, Mangone M

Abstract

Preclinical Research Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that is frequently characterized by the constitutive expression of the oncogenic protein BCR-ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) targeting breakpoint cluster region-ABL are the first-line therapy for most CML patients and have drastically improved the prognosis of CML. However, some CML patients are unresponsive to TKI treatment, and a notable proportion of initially responsive patients develop drug resistance. Several molecular pathways have been correlated with resistance to TKI treatment, however, the exact mechanism of developing drug resistance remains ambiguous. Recently, microRNAs (miRNAs) have been implicated in the progression of CML and the development of resistance to TKI treatment based on their important regulatory function in cell homeostasis, and the deregulation observed in the initiation and progression of many leukemia subtypes. In this review, we summarize some of the major discoveries regarding miRNAs in CML, and their relevance as biomarkers for diagnosis, disease progression, and drug sensitivity. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.

PMID: 26284455 [PubMed - as supplied by publisher]

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[Pharmacokinetic issues on cancer pharmacotherapy].

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[Pharmacokinetic issues on cancer pharmacotherapy].

Nihon Rinsho. 2015 Aug;73(8):1357-63

Authors: Tanigawara Y

Abstract

Efficacy of cancer pharmacotherapy depends upon drug exposure to the body and responsiveness of the tumor to the drug treatment. Drug exposure is determined by pharmacokinetics and dose, whereas responsiveness is intrinsically variable by tumor heterogeneity. Molecular targeting drugs are used as promising therapy for cancers, and most of them are coupled with particular diagnostics which can predict responders and non-responders before treatment. On the other hand, lower drug exposure to the body can lead to insufficient efficacy. A number of important evidences have been published recently on exposure-response relationships for molecular targeting drugs including monoclonal antibodies and small molecules. In this chapter, two examples are presented; anti-HER2 antibody and tyrosine kinase inhibitor. Patients with the lowest trough concentrations of trastuzumab in cycle 1 showed shorter overall survival in metastatic gastric cancer study. Efficacy of imatinib in chronic myelogenous leukemia depended on plasma concentration of imatinib, and therapeutic drug monitoring (TDM) of imatinib is expected to improve the therapeutic outcome in CML.

PMID: 26281690 [PubMed - in process]

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A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia.

Posted by rob on August 17, 2015 under Uncategorized | Comments are off for this article

A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia.

Eur J Haematol. 2015 Aug 16;

Authors: Crysandt M, Kramer M, Ehninger G, Bornhäuser M, Berdel WE, Serve H, Röllig C, Kaifie A, Jost E, Brummendorf TH, Wilop S

Abstract

Overweight and obese patients have an increased risk to develop several malignancies and, additionally, body mass index (BMI) impacts on outcome in several solid tumors. However, little is known for AML. We analyzed a cohort of 3526 AML patients treated in three prospective multicenter trials within the German Study Alliance Leukemia. In multivariate analysis, we identified BMI as an independent risk factor for both DFS (HR 1.014, p=0.0217) and OS (HR 1.015, p<0.0036). Interestingly, overweight and obesity seemed to be a risk factor predominantly in patients with de novo AML younger than 65 years with intermediate risk and adverse cytogenetics. Overweight with a BMI ?25kg/m² best discriminated worse outcome and led to an absolute reduction of long term survival of 5-7% in the group of all younger patients (3-year OS 39.9% vs. 47.3%; 10-year OS 28.7% vs. 33.8%, p=0.0002). Additionally, response to induction therapy was significantly reduced in these patients (76.9% vs. 82.8%, p<0.0001). Thus, in younger patients with de novo AML, overweight and obesity are risk factors for impaired response to induction therapy, DFS and OS. This effect is, in part but not fully, explained by dose reduction such as dose capping at a body surface area of 2m². This article is protected by copyright. All rights reserved.

PMID: 26277604 [PubMed - as supplied by publisher]

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Total hip arthroplasty in very young bone marrow transplant patients.

Posted by rob on August 15, 2015 under Uncategorized | Comments are off for this article

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Total hip arthroplasty in very young bone marrow transplant patients.

J Surg Orthop Adv. 2015;24(2):99-104

Authors: Ledford CK, Vap AR, Bolognesi MP, Wellman SS

Abstract

Concerns remain about total hip arthroplasty (THA) performed in very young patients, especially those with complex medical history such as allogeneic bone marrow transplantation (ABMT). This study retrospectively reviews the perioperative courses and functional outcomes of ABMT patients <21 years old undergoing primary uncemented THA. Nine THAs were performed in five ABMT patients at an average age of 19.7 years. The interval between ABMT and THA was 73.0 months with clinical follow-up of 25.8 months. Harris Hip Scores (HHS) increased dramatically from preoperatively 44.5 (range, 31.1-53.4) to postoperatively 85.2 (range, 72.0-96.0) and all patients subjectively reported a good (four hips) to excellent (five hips) overall outcome. There was one reoperation for periprosthetic fracture fixation but there were no infections or revisions performed. Despite the history of severe hematopoietic conditions requiring ABMT, these very young patients do appear to have improved pain and function following primary THA with short-term follow-up.

PMID: 25988690 [PubMed - indexed for MEDLINE]

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Epidemiologic Investigation of a Cluster of Neuroinvasive Bacillus cereus Infections in 5 Patients With Acute Myelogenous Leukemia.

Posted by rob on August 14, 2015 under Uncategorized | Comments are off for this article

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Epidemiologic Investigation of a Cluster of Neuroinvasive Bacillus cereus Infections in 5 Patients With Acute Myelogenous Leukemia.

Open Forum Infect Dis. 2015 Sep;2(3):ofv096

Authors: Rhee C, Klompas M, Tamburini FB, Fremin BJ, Chea N, Epstein L, Halpin AL, Guh A, Gallen R, Coulliette A, Gee J, Hsieh C, Desjardins CA, Pedamullu CS, DeAngelo DJ, Manzo VE, Folkerth RD, Milner DA, Pecora N, Osborne M, Chalifoux-Judge D, Bhatt AS, Yokoe DS

Abstract

Background. ?Five neuroinvasive Bacillus cereus infections (4 fatal) occurred in hospitalized patients with acute myelogenous leukemia (AML) during a 9-month period, prompting an investigation by infection control and public health officials. Methods. ?Medical records of case-patients were reviewed and a matched case-control study was performed. Infection control practices were observed. Multiple environmental, food, and medication samples common to AML patients were cultured. Multilocus sequence typing was performed for case and environmental B cereus isolates. Results. ?All 5 case-patients received chemotherapy and had early-onset neutropenic fevers that resolved with empiric antibiotics. Fever recurred at a median of 17 days (range, 9-20) with headaches and abrupt neurological deterioration. Case-patients had B cereus identified in central nervous system (CNS) samples by (1) polymerase chain reaction or culture or (2) bacilli seen on CNS pathology stains with high-grade B cereus bacteremia. Two case-patients also had colonic ulcers with abundant bacilli on autopsy. No infection control breaches were observed. On case-control analysis, bananas were the only significant exposure shared by all 5 case-patients (odds ratio, 9.3; P = .04). Five environmental or food isolates tested positive for B cereus, including a homogenized banana peel isolate and the shelf of a kitchen cart where bananas were stored. Multilocus sequence typing confirmed that all case and environmental strains were genetically distinct. Multilocus sequence typing-based phylogenetic analysis revealed that the organisms clustered in 2 separate clades. Conclusions. ?The investigation of this neuroinvasive B cereus cluster did not identify a single point source but was suggestive of a possible dietary exposure. Our experience underscores the potential virulence of B cereus in immunocompromised hosts.

PMID: 26269794 [PubMed]

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ERK2-PYRUVATE KINASE AXIS PERMITS PMA-INDUCED MEGAKARYOCYTE DIFFERENTIATION IN K562 CELLS.

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ERK2-PYRUVATE KINASE AXIS PERMITS PMA-INDUCED MEGAKARYOCYTE DIFFERENTIATION IN K562 CELLS.

J Biol Chem. 2015 Aug 12;

Authors: Chaman N, Iqbal MA, Siddiqui FA, Gopinath P, Bamezai RN

Abstract

Metabolic changes that contribute to differentiation are not well understood. Overwhelming evidence shows critical role of glycolytic enzyme pyruvate kinase (PK) in directing metabolism of proliferating cells. However, its role in metabolism of differentiating cells is unclear. Here we studied the role of PK in phorbol 12-myristate 13-acetate (PMA) induced megakaryocytic differentiation in human leukemia K562 cells. We observed that PMA treatment decreased cancer-type anabolic metabolism but increased ATP production, along with upregulated expression of two PK isoforms (PKM2 and PKR) in an ERK2 dependent manner. Interestingly, silencing of PK (PKM2 and PKR) inhibited PMA-induced megakaryocytic differentiation, as revealed by decreased expression of megakaryocytic differentiation marker CD61 and cell cycle behaviour. Further, PMA-induced ATP production reduced greatly upon PK silencing, suggesting that PK is required for ATP synthesis. Besides metabolic effects, PMA treatment also translocated PKM2, but not PKR, into nucleus. ERK1/2 knockdowns independently and together suggested the role of ERK2 in the upregulation of both the isoforms of PK, proposing a role of ERK2-PK isoform axis in differentiation. Collectively, our findings unravel ERK2 guided PK-dependent metabolic changes during PMA induction, which are important in megakaryocytic differentiation.

PMID: 26269597 [PubMed - as supplied by publisher]

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Patients with Philadelphia-positive leukemia with BCR-ABL kinase mutations before allogeneic transplantation predominantly relapse with the same mutation.

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Patients with Philadelphia-positive leukemia with BCR-ABL kinase mutations before allogeneic transplantation predominantly relapse with the same mutation.

Biol Blood Marrow Transplant. 2015 Jan;21(1):184-9

Authors: Egan DN, Beppu L, Radich JP

Abstract

Despite the successes of tyrosine kinase inhibitors (TKIs) in improving outcomes in patients with chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL), allogeneic hematopoietic stem cell transplantation (HSCT) continues to be an important and potentially curative option for selected patients with either disease. After HSCT, TKIs are increasingly being used to treat or prevent disease relapse, and practice patterns suggest that these TKIs are often chosen empirically without regard to pre-HSCT mutation status. We investigated whether ABL kinase domain mutations persist after transplantation and, thus, whether pre-HSCT mutation status should inform the selection of post-HSCT TKIs in these patients. We retrospectively analyzed adults who underwent allogeneic HSCT for CML and Ph + ALL at our institution between 2000 and 2010, and we identified subjects who had detectable BCR-ABL transcripts by polymerase chain reaction (PCR), as well as available RNA for Sanger sequencing of the ABL kinase domain, in both the pre- and post-HSCT settings. In total, 95 CML and 20 Ph + ALL patients with positive PCR transcripts were identified, of which 10 (10.5%) and 4 (20.0%), respectively, were found to have pre-HSCT ABL kinase mutations known to confer TKI resistance. In 9 (64.2%) of these 14 patients, the same kinase mutation was also detectable at an average time of 191 days after HSCT. Seven (50.0%) of the 14 harboring mutations had relapsed/refractory disease by last follow-up, of which, in retrospect, 6 had received a predictably ineffective TKI within the first 100 days after transplantation based on our mutation analysis. These data support the idea that pre-existing mutations in the ABL kinase domain, frequently associated with resistance to TKIs and prevalent in a transplantation population, are persistently detectable in the majority of patients after transplantation. We propose that such resistance patterns should be considered when selecting TKIs in the post-HSCT setting, including clinical trials of post-HSCT TKI prophylaxis.

PMID: 25300870 [PubMed - indexed for MEDLINE]

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Long-term survival after transplantation of unrelated donor peripheral blood or bone marrow hematopoietic cells for hematologic malignancy.

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Long-term survival after transplantation of unrelated donor peripheral blood or bone marrow hematopoietic cells for hematologic malignancy.

Biol Blood Marrow Transplant. 2015 Jan;21(1):55-9

Authors: Eapen M, Logan BR, Appelbaum FR, Antin JH, Anasetti C, Couriel DR, Chen J, Maziarz RT, McCarthy PL, Nakamura R, Ratanatharathorn V, Vij R, Champlin RE

Abstract

We sought to determine whether differences in chronic graft-versus-host disease (GVHD) rates would lead to survival differences by comparing 2463 peripheral blood (PB) and 1713 bone marrow (BM) hematopoietic cell transplant recipients. Patients had acute leukemia, chronic myeloid leukemia (CML), or myelodysplastic syndrome, and they received myeloablative conditioning regimens and calcineurin-inhibitor GVHD prophylaxis. There were no significant differences in long-term survival after transplantation of PB and BM, except for patients in first chronic phase CML. For these patients, the 5-year rate of survival was lower after transplantation of PB compared with transplantation of BM (35% versus 56%, P = .001). Although mortality risks were higher in patients with chronic GVHD after both PB (hazard ratio [HR], 1.58; P < .001) and BM (HR 1.73; P < .001) transplantations, its effect on mortality did not differ by graft type (P = .42). BM is the preferred graft for first chronic phase CML, whereas as either graft is suitable for other leukemias.

PMID: 25255165 [PubMed - indexed for MEDLINE]

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Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia.

Posted by rob on August 13, 2015 under Uncategorized | Comments are off for this article

Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia.

Bioorg Med Chem Lett. 2015 Jul 26;

Authors: Muthyala R, Shin WS, Xie J, Sham YY

Abstract

Histone deacetylase (HDAC) is a validated target for pursuing anticancer agents. However, obtaining a selective inhibitor against a given HDAC member remains a significant challenge. We report here the use of 1-hydroxypyridine-2-thione (1HPT) as a key pharmacophore for zinc-binding can result in highly selective HDAC inhibitors. 1HPT-6-carboxylic acid exhibits selective inhibition of HDAC6 with an IC50 of 150nM that corresponds to a remarkable 0.9 ligand efficiency. Two analogs with simple amino acids shows nearly 600-fold selectivity among the eleven zinc-dependent HDACs. At low micromolar concentration these compounds inhibit the growth of HDAC8-overexpressing chronic myelogenous leukemia cells and specific form of acute myelogenous leukemia cells. Their potential mode of binding was examined by molecular docking and their stability was assessed in mouse and human plasma. Together the results suggest 1HPT analogs exhibit promising therapeutic potential for further development as anticancer agents to treat leukemia.

PMID: 26264503 [PubMed - as supplied by publisher]

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[CHRONIC MYELOID LEUKEMIA IN A YOUNG MALE PRESENTING WITH BILATERAL CALF PAIN DUE TO LEUKOSTASIS].

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[CHRONIC MYELOID LEUKEMIA IN A YOUNG MALE PRESENTING WITH BILATERAL CALF PAIN DUE TO LEUKOSTASIS].

Harefuah. 2015 May;154(5):296-8, 340

Authors: Rottenstreich M, Lavie M, Rottenstreich A

Abstract

Chronic myeloid Leukemia (CML) is a chronic myeloproliferative disorder, caused by the unregulated proliferation of granulocytes at different stages of development and maturation. Leukostasis is one of the complications of CML, causing partial or total occlusion of microvasculature with a variety of clinical manifestations, mostly ophthalmic, neurologic or respiratory. Recently, we encountered a 21-year old soldier, who complained of severe bilateral calf pain which began a few months earlier during training. He underwent complete ambulatory orthopedic evaluation which was unrevealing, and finally presented to the hospital casualty department where CML was diagnosed on the basis of an elevated WBC count and morphologic findings. Bilateral retinal hemorrhages due to leukostasis were noticed at fundoscopy. The calf pain resolved completely after leukapheresis and initial cytoreductive therapy and was in retrospect attributed to peripheral leukostasis. To the best of our knowledge this is the first report of CML presenting with bilateral calf pain due to Leukocytosis and possible leukostasis. This case report highlights the importance of differential diagnosis in cases of calf pain and the awareness of this rare manifestation of CML.

PMID: 26168638 [PubMed - indexed for MEDLINE]

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Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia.

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Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia.

Blood. 2015 Jun 4;125(23):3618-26

Authors: Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L, Morabito M, Met E, Debord C, Benayoun E, Nloga AM, Fenaux P, Braun T, Willekens C, Quesnel B, Adès L, Fontenay M, Rameau P, Droin N, Koscielny S, Solary E, Francophone Myelodysplasia Group

Abstract

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/ myeloproliferative neoplasm whose diagnosis is currently based on the elevation of peripheral blood monocytes to >1 × 10(9)/L, measured for ?3 months. Diagnosis can be ambiguous; for example, with prefibrotic myelofibrosis or reactive monocytosis. We set up a multiparameter flow cytometry assay to distinguish CD14(+)/CD16(-) classical from CD14(+)/CD16(+) intermediate and CD14(low)/CD16(+) nonclassical monocyte subsets in peripheral blood mononucleated cells and in total blood samples. Compared with healthy donors and patients with reactive monocytosis or another hematologic malignancy, CMML patients demonstrate a characteristic increase in the fraction of CD14(+)/CD16(-) cells (cutoff value, 94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort (307 samples), respectively. The accumulation of classical monocytes, which demonstrate a distinct gene expression pattern, is independent of the mutational background. Importantly, this increase disappears in patients who respond to hypomethylating agents. We conclude that an increase in the fraction of classical monocytes to >94.0% of total monocytes is a highly sensitive and specific diagnostic marker that rapidly and accurately distinguishes CMML from confounding diagnoses.

PMID: 25852055 [PubMed - indexed for MEDLINE]

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Genes and childhood leukemia.

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Genes and childhood leukemia.

Postepy Hig Med Dosw (Online). 2015;69:302-8

Authors: K?sy J, Januszkiewicz-Lewandowska D

Abstract

Leukemia is a heterogeneous hematologic malignancy originating from a multipotent hematopoietic stem cell. It ranks among the commonest cancers in childhood and is characterized by excessive proliferation and differentiation block. The process of leukemogenesis is governed by genetic changes at both the cytogenetic and molecular level. According to numerous analyses, a large spectrum of mutations and rearrangements underlying the disease affect essential cellular transduction pathways, genes ensuring proper course of hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators. Common lesions include translocations to T cell receptor (TCR) loci in T-lineage acute lymphoblastic leukemia (T-ALL), mutations of transcription factors regulating B-lineage development and cell maturation in B-lineage acute lymphoblastic leukemia (B-ALL) (PAX5, TCF3, EBF1, etc.), aberrational disruption of genes coding for transcription factors and coactivators in acute myeloid leukemia (AML) (e.g. CBF) or BCR-ABL1 fusion and activation of multiple kinases in chronic myeloid leukemia (CML). These alterations severely impair cell function. Broadening knowledge of the genetic background gives an insight into the pathobiology of a disease and allows for a better understanding of it. An appropriate investigation of genomic events yields diagnostic, prognostic and therapeutic implications. Broadening knowledge of the pathogenesis of leukemia seems to be a promising contribution to precise stratification of patients, reducing the toxicity and adverse effects caused by medical intervention, treatment personalization and introduction of targeted therapy accessible to a wide range of patients.

PMID: 25748621 [PubMed - indexed for MEDLINE]

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The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells.

Posted by rob on August 12, 2015 under Uncategorized | Comments are off for this article

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The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells.

Leukemia. 2015 Aug 11;

Authors: Nishioka C, Ikezoe T, Takeuchi A, Nobumoto A, Tsuda M, Yokoyama A

Abstract

The aim of this study was to explore the biological functions of a tetraspanin family protein CD82 expressed aberrantly in chemotherapy-resistant CD34(+)/CD38(-) acute myelogenous leukemia (AML) cells. Microarray analysis of patient-isolated CD34(+)/CD38(-) AML cells revealed that the levels of anti-apoptotic protein BCL2L12 were downregulated after CD82 depletion by specific shRNA. Western blot analysis indicated that BCL2L12 was aberrantly expressed in patient-isolated AML cells and AML cell lines. Furthermore, CD82 blockade by a specific antibody downregulated BCL2L12 in parallel with de-phosphorylation of STAT5 and AKT, while pharmacological inhibition of STAT5 and AKT activation decreased BCL2L12 expression in leukemia cells. In addition, shRNA-mediated downregulation of BCL2L12 increased the levels of cleaved caspase 3 and suppressed proliferation of leukemia cells, impairing their engraftment in immunodeficient mice. Taken together, our results indicate that CD82 regulated BCL2L12 expression via STAT5A and AKT signaling and stimulated proliferation and engrafting of leukemia cells, suggesting that CD82 and BCL2L12 may be promising therapeutic targets in AML.Leukemia accepted article preview online, 11 August 2015. doi:10.1038/leu.2015.219.

PMID: 26260387 [PubMed - as supplied by publisher]

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The V-val subtype Epstein-Barr virus nuclear antigen 1 promotes cell survival after serum withdrawal.

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The V-val subtype Epstein-Barr virus nuclear antigen 1 promotes cell survival after serum withdrawal.

Oncol Rep. 2015 Feb;33(2):958-66

Authors: Chao M, Wang HN, Lu YJ, Chang YS, Yu JS

Abstract

Epstein-Barr virus (EBV) can establish latent infection and has been associated with various human cancers. Epstein-Barr nuclear antigen 1 (EBNA1) is the only viral protein that is expressed in all EBV-associated malignant tissues. The N- and C-terminal domains of EBNA1, which are connected by internal glycine/alanine-rich short repeat sequences of various sizes, show sequence divergence across EBV strains isolated from around the world. At least five subtypes have been described, according to the amino acid at residue 487: P-ala, P-thr, V-val, V-pro, and V-leu. Whether the variations of EBNA-1 contribute to the pathogenesis of EBV or simply reflect the geographical distribution of EBV remain to be investigated. Furthermore, the cell effects conferred by EBNA1 subtypes that differ from that of the B95.8 prototype, which belongs to the P-ala subtype, remain to be elucidated. In this study, PCR was amplified with the full-length V-val EBNA1 gene from the CG3 cell line, an EBV-carrying lymphoblastoid cell line derived from a Taiwanese chronic myeloid leukemia patient. Plasmids expressing His-tagged EBNA1 fusion proteins in E. coli were constructed and used to raise antibodies in rabbit. The V-val EBNA1 gene was then cloned into a eukaryotic expression vector and successfully expressed in the transfected cultured cells. Expression of V-val EBNA1 rendered 293 cells able to undergo serum?independent cell proliferation, providing them with anti-apoptotic abilities, which are two characteristics of cancer cells. These data suggested that use of EBNA1 originally derived from tumor cells, rather than the more commonly utilized prototype, when investigating the potential role of EBNA1 in the oncogenesis of EBV-associated malignancies, is crucial.

PMID: 25434292 [PubMed - indexed for MEDLINE]

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Q192R and L55M Polymorphisms of Paraoxonase 1 Gene in Chronic Myelogenous Leukemia and Chronic Lymphocytic Leukemia.

Posted by rob on August 9, 2015 under Uncategorized | Comments are off for this article

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Q192R and L55M Polymorphisms of Paraoxonase 1 Gene in Chronic Myelogenous Leukemia and Chronic Lymphocytic Leukemia.

Anticancer Res. 2015 Sep;35(9):4807-12

Authors: Tomatir AG, Pehlivan S, Sahin HH, Balci SO, Budeyri S, Pehlivan M

Abstract

AIM: The aim of the present study was to investigate the association between Paraoxonase 1 (PON1) gene polymorphisms Q192R, and L55M in patients with Chronic Myelogenous Leukemia (CML) and Chronic Lymphocytic Leukemia (CLL) patients.

MATERIALS AND METHODS: We analyzed samples from 60 patients with CML, 60 with CLL and 84 healthy controls. Polymerase Chain Reaction (PCR) – Restriction Fragment Length Polymorphism (RLFP) was performed and samples were run in agarose gel.

RESULTS: We found statistically significant results showing an increase in both the RR genotype (p=0.044) and the R allele (p=0.011) for PON1 Q192R, and an increase in the MM genotype (p=0.007) and a decrease in the LL genotype (p=0.004) and R allele (p=0.001) in PON1 L55M in patients with CLL.

CONCLUSION: We concluded that both the Q192R gene polymorphism with an increase in the genotype R allele, and the M/L55 with an increase in the MM genotype play a role in CLL susceptibility, and a decrease in the LL genotype can act against disease in the Turkish population.

PMID: 26254371 [PubMed - in process]

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Invasive Fungal Infections in Pediatric Acute Myelogenous Leukemia.

Posted by rob on August 8, 2015 under Uncategorized | Comments are off for this article

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Invasive Fungal Infections in Pediatric Acute Myelogenous Leukemia.

Pediatr Infect Dis J. 2015 Aug 6;

Authors: Ducassou S, Rivaud D, Auvrignon A, Vérité C, Bertrand Y, Gandemer V, Leverger G

Abstract

This study investigated invasive fungal infections (IFI) in patients with acute myelogenous leukemia who were included in the ELAM 02 protocol between 2005 and 2011. Among 387 patients, 15 had aspergillosis, 9 had candidiasis and 2 had mucormycosis. The most frequent localization was lung.After a median of 34 months, 2 deaths were attributable to IFI withoutany difference in survival between the groups with and without IFI.

PMID: 26252569 [PubMed - as supplied by publisher]

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18F-FDG PET/CT of Primary Cervical Granulocytic Sarcoma.

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18F-FDG PET/CT of Primary Cervical Granulocytic Sarcoma.

Clin Nucl Med. 2015 Aug 6;

Authors: Zheng LC, OuYang XL, Zhang WJ, Liu GC, Zhang XM

Abstract

Granulocytic sarcoma is an uncommon solid extramedullary tumor composed of immature leukocytes and commonly associated with acute myelogenous leukemia. Isolated granulocytic sarcoma in the cervix of uterus is exceedingly rare. Hereby we describe a case of FDG PET/CT finding of cervical granulocytic sarcoma without acute myelogenous leukemia in a 51-year-old patient.

PMID: 26252324 [PubMed - as supplied by publisher]

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MRP1 and P-glycoprotein expression assays would be useful in the additional detection of treatment non-responders in CML patients without ABL1 mutation.

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MRP1 and P-glycoprotein expression assays would be useful in the additional detection of treatment non-responders in CML patients without ABL1 mutation.

Leuk Res. 2015 Jul 23;

Authors: Park SH, Park CJ, Kim DY, Lee BR, Kim YJ, Cho YU, Jang S

Abstract

We evaluated the ability of the rhodamine-123 efflux assay, multidrug resistance-associated protein-1 (MRP1) expression assay and P-glycoprotein (Pgp) expression assay to discriminate chronic myelogenous leukemia (CML) patients who had failed treatment or were at risk of failure. Each assay was performed in blood samples from CML patients (n=224) treated with tyrosine kinase inhibitors, taken at diagnosis (n=14) and follow-up (n=210). Patient samples were categorized as optimal response (n=120), suboptimal response (n=54), and treatment failure (n=36). Treatment-failed patients had a significantly higher MRP1 expression (5.24% vs. 3.54%, P=0.006) and Pgp expression (5.25% vs. 3.48%, P=0.005) than responders. Both MRP1 (%) and Pgp (%) were highly specific (95.2% and 94.5%) and relatively accurate (83.0% and 82.5%) in the detection of treatment non-responders. Of treatment-failed patients, 41.2% had a positive result in at least one assay and of these patients without ABL1 kinase domain mutation, 51.9% were positive in at least one assay. However, the rhodamine-123 efflux assay failed to discriminate two patient groups. Thus, both MRP1 and Pgp expression assays could be useful for additional identification of treatment non-responders in CML patients without ABL1 mutation.

PMID: 26248945 [PubMed - as supplied by publisher]

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Acquired generalized ichthyosis in chronic myeloid leukaemia.

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Acquired generalized ichthyosis in chronic myeloid leukaemia.

Natl Med J India. 2014 Sep-Oct;27(5):291

Authors: Vinod KV, Verma S

PMID: 26037441 [PubMed - indexed for MEDLINE]

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