Posted by rob on April 14, 2011 under Uncategorized | 
Cytomegalovirus sinusitis in a child with chronic myelogenous leukemia following bone marrow transplantation.
Pediatr Blood Cancer. 2011 Jul 1;56(7):1140-2
Authors: Rayes A, Sahni K, Hanna C, Suryadevara M, Goyal P, Cherrick I
Cytomegalovirus (CMV) is a common opportunistic pathogen. CMV sinusitis has been described in acquired immunodeficiency syndrome (AIDS) patients, but not in other immune compromising conditions. In this report, we describe CMV sinusitis in a child with chronic myelogenous leukemia (CML) following bone marrow transplantation. Pediatr Blood Cancer 2011;56:1140-1142. © 2011 Wiley-Liss, Inc.
PMID: 21488162 [PubMed - in process]
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A pyrosequencing-based test for detection and relative quantification of the BCR-ABL1 T315I point mutation.
J Clin Pathol. 2011 Apr 12;
Authors: Schumacher JA, Szankasi P, Bahler DW, Ho AK, Kelley TW
Aims The BCR-ABL1 T315I mutation imparts resistance to tyrosine kinase inhibitors currently available for treatment of chronic myelogenous leukaemia. Thus, quantitative monitoring of the emergence and expansion of T315I-positive subclones may be clinically useful. The goals of this study were to retrospectively review the authors’ experience with Sanger sequencing-based BCR-ABL1 kinase domain mutation testing, paying particular attention to the T315I mutation, and to develop an alternative test for relative quantification of T315I using pyrosequencing. Methods The performance of a new T315I pyrosequencing assay was evaluated. Total RNA was isolated from whole blood and reverse-transcribed. The resulting cDNA was subjected to an initial round of PCR across the BCR-ABL1 breakpoint followed by a second round to amplify the sequence flanking ABL1 codon 315. The final PCR product was pyrosequenced to detect and quantify the T315I point mutation. Additional experiments were carried out to determine the effects of background untranslocated ABL1 on assay sensitivity in samples with low tumour burden. Results The results show that T315I was the most commonly detected kinase domain mutation and was persistent in follow-up testing. All 26 specimens that tested positive by Sanger sequencing for the T315I mutation were also positive using the pyrosequencing test. Relative quantification data derived from pyrosequencing matched the approximate wild-type/mutant ratios found by Sanger sequencing. Serial dilution experiments show sensitivity to 5% mutant allele. The authors also quantitatively assessed the influence of untranslocated ABL1 in the sample background on the assay and found that it occurred at levels not likely to influence performance. Conclusion The described test is useful for detection and relative quantification of the T315I point mutation in chronic myelogenous leukaemia in a sensitive, specific and reproducible manner.
PMID: 21486895 [PubMed - as supplied by publisher]
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Prophylaxis and treatment of invasive aspergillosis with voriconazole, posaconazole and caspofungin – review of the literature.
Eur J Med Res. 2011 Apr 28;16(4):145-52
Authors: Karthaus M
Major progress for the management of invasive aspergillosis has come from the introduction of new antifungals since the late 1990s. Although mortality of invasive aspergillosis remains as high as 30-50%. Backbone of management are prophylaxis, early diagnosis and early initiation of antifungals for reduction of invasive aspergillosis related mortality. Randomized trials have been undertaken for the prophylaxis as well as treatment of invasive aspergillosis in the last two decades. Posaconazole is recommended for prophylaxis against aspergillosis in patients treated for acute myelogenous leukemia, myelodysplastic syndrome or patients with graft versus host disease after allogeneic transplantation. Efficacy has been shown for first-line therapy of invasive aspergillosis with voriconazole and liposomal amphotericin B. Gastrointestinal resorption for the azoles posaconazole, voriconazole and itraconazole differ considerably. While oral voriconazole resportion is reduced when taken with food, posaconazole has to be taken with fatty food for optimal intestinal resorption. Beside all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state of prophylaxis and treatment of invasive aspergillosis and points out clinicians unmet needs.
PMID: 21486728 [PubMed - in process]
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Authors: J Lu, Y Ma, N Kong, Z Alipio, C Gao, D S Krause, L E Silberstein
& L Chai (Source: Leukemia)
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In this study, we sought to identify targeted PKR activation by Bcr-Abl AS RNA, an anti-sense RNA complementary to the unique mRNA fragments flanking the fusion point of Bcr-Abl, which can be used as an effective anti-leukemia strategy in K562 cells. Moreover, we observed expression of Bcr-Abl AS RNA in K562 cells which resulted in selective apoptosis induction through specific activation of PKR, leading to phosphorylation of eIF2?, global inhibition of protein synthesis, caspase-8 activation and BAX up-regulation. The targeted PKR activation and induced apoptosis were reversed by the PKR inhibitor 2-aminopurine. Taken together, our results indicate that targeted PKR activation led to selective apoptosis induction in K562 cells, which correlated with caspase-8 activity and enhanced ex…
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