Posted by rob on February 1, 2012 under Uncategorized | 
CONCLUSIONS: Dasatinib was an effective treatment with the potential to improve long-term outcomes for patients with newly diagnosed CML-CP.
PMID: 22285209 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
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This report describes a case that exemplifies caregiving burden and discusses the importance of identifying caregivers at risk of negative health outcomes and intervening to attenuate the stress associated with the caregiving experience. (Source: JAMA)
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Conclusions: The unfavorable trend in outcome for adolescent and young adult with chronic myeloid leukemia is unexpected. Additional research in this population is required to better define outcomes, understand the cause of this difference, and to help make better treatment recommendations.
PMID: 22271898 [PubMed - as supplied by publisher] (Source: Haematologica)
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Authors: Itonaga H, Tsushima H, Hata T, Matsuo E, Imanishi D, Imaizumi Y, Kawaguchi Y, Fukushima T, Doi Y, Mori S, Kamihira S, Tomonaga M, Miyazaki Y
Abstract
The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (…
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Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways.
Leukemia. 2012 Jan 13;
Authors: Piazza F, Manni S, Ruzzene M, Pinna LA, Gurrieri C, Semenzato G
Abstract
CK2 is a multitask kinase whose role is essential for a countless number of cellular processes, many of which are critical for blood cell development. A prevailing task for this kinase rests on counteracting programmed cell death triggered by multiple stimuli. CK2 is overexpressed in many solid tumors and in vivo mouse models have proven its tumorigenic potential. Recent data have suggested that CK2 may also have a significant role in the pathogenesis of hematopoietic tumors, such as multiple myeloma, chronic lymphocytic leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia and chronic myeloproliferative neoplasms. CK2 regulates hematopoiesis-associated signaling pathways and seems to reinforce biochemical cascades indispensable for tumor growth, proliferation and resistance to conventional and novel cytotoxic agents. Although its activity is multifold, recent evidence supports the rationale of CK2 inhibition as a therapeutic strategy in solid and hematological tumors and phase-I clinical trials are in progress to test the efficacy of this innovative therapeutic approach. In this review, we will summarize the data supporting CK2 as an oncogenic kinase in blood tumors and we will describe some critical signaling pathways, whose regulation by this protein kinase may be implicated in tumorigenesis.Leukemia advance online publication, 13 January 2012; doi:10.1038/leu.2011.385.
PMID: 22289987 [PubMed - as supplied by publisher]
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Clinical applications of epigenetic markers and epigenetic profiling in myeloid malignancies.
Semin Oncol. 2012 Feb;39(1):109-22
Authors: McDevitt MA
Abstract
Aberrant DNA methylation is frequent in the myeloid malignancies, particularly myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Promoter CpG methylation is correlated with silencing of tumor-suppressor genes (TSGs) in specific pathways that are also targets of mutation or other mechanisms of inactivation, and is thought to contribute to disease progression and poor prognosis. Epigenetic contributions to myeloid pathogenesis are more complex. Examples include TSG inactivation and oncogenic activation associated with formation of altered chromatin separate from CpG methylation. Epigenetic dysregulation occurs at multiple disease stages and at non-CpG island genomic sites, and also includes genomic hypomethylation and small RNA mechanisms of epigenetic regulation. Identification of recurrent mutations in potential epigenetic regulators, including TET2, IDH1, IDH2, DNMT3A, UTX, and ASXL1, were recently described. Accordingly, therapeutics directed towards epigenetic mechanisms including methylation inhibitors and histone deacetylase (HDAC) inhibitors have had some clinical success when applied to MDS and AML. However, identification of the underlying mechanisms associated with clinical responses and drug resistance remain enigmatic. Remarkably, in spite of significant molecular and translational progress, there are currently no epigenetic biomarkers in widespread clinical use. In this review, we explore the potential applications of epigenetic biomarker discovery, including epigenetic profiling for myeloid malignancy pathogenesis understanding, diagnostic classification, and development of effective treatment paradigms for these generally considered poor prognosis disorders.
PMID: 22289497 [PubMed - in process]
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Imatinib and beyond – targeting activated tyrosine kinases in myeloproliferative disorders.
Onkologie. 2012;35 Suppl 1:34-41
Authors: Hochhaus A, Reiter A, Ernst T, La Rosée P
Abstract
Tyrosine kinases (TKs) play a major role in cellular signal transduction. Deregulated TK activity has been observed in solid cancers and hematologic malignancies. Advances in the understanding of the oncogenic activation of TKs led to the identification of new kinase inhibitors with improved potency, specificity, and efficacy. With the advent of imatinib mesylate, a new era in the management of patients with BCR-ABL+ chronic myelogenous leukemia (CML), gastrointestinal stromal tumors, and myeloproliferative neoplasms including chronic myelomonocytic leukemia with PDGFRB gene rearrangements and hypereosinophilic syndrome has begun. CML represents a model for the rational design of TK inhibitors based on the insights into signal transduction pathways. In CML, treatment with imatinib led to an outstanding clinical efficacy with limited toxicity. In BCR-ABL-negative myeloproliferation, the finding of activating point mutations in JAK2 prompted the development of JAK inhibitors to target this activated pathway. Aberrations of epigenetically active genes are the latest finding in the pathogenesis of myeloproliferative disorders and will serve as another target for innovative therapies.
PMID: 22286586 [PubMed - in process]
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Recent developments and future perspectives of personalized oncology.
Onkologie. 2012;35 Suppl 1:4-7
Authors: Grüllich C, von Kalle C
Abstract
Increasing understanding of molecular carcinogenesis has begun to change paradigms in oncology. On the diagnostic side, the characterization of key mutations and molecular pathways responsible for tumor development and progression has led to the identification of a large number of potential targets for diagnostic and therapeutic intervention. On the treatment and prevention side, molecular analysis will be of even greater importance for guiding individualized therapy. Diagnostics of molecular lesions present in each tumor will become a key feature of future clinical care. This will allow prediction of response with substantially increased accuracy, stratification of particular patient groups, and eventually personalization of therapy. Striking examples of molecular targeted therapies that have already been established in clinical practice include tyrosine kinase inhibitors in chronic myelogenous leukemia and gastrointestinal stromal tumors, epidermal growth factor receptor (EGFR) inhibition in EGFR-mutated lung cancer, HER2/neu blockade in HER2/neu-positive breast cancer, and anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALK fusion. The scientific development along this line will change the approach to tumor diseases in the future. Patients will be treated according to the specific molecular profiles found in the individual tumor tissue and preferentially with targeted substances, if available.
PMID: 22286581 [PubMed - in process]
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