Ethical Implication Of Multiple Myeloma

Multiple myeloma (also plasma cell myeloma also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease) is a progressive hematologic (blood) disease. It is a cancer of the plasma cell, an important part of the immune system that produces immunoglobulins (antibodies) to help fight infection and disease.

Advances in MDS therapy will derive from molecular precision and identification of potential druggable targets for the disease. In 2005, The Cancer Genome Atlas (TCGA), and during 2008, The International Cancer Genome Consortium (ICGC) were designed as large-scale projects to improve understanding of cancer associated recurrent somatic mutations. In AML, robust prognostic relevant mutations were reported with mutational subgroups frequently observed in MDS suggesting similar ability to detect a significant impact on MDS outcome. Seven subgroups including activating signaling, DNA methylation, chromatin modifiers, spliceosome, myeloid transcription factors, tumor suppressor genes, and less commonly observed mutations including cohesin complex, BCOR, and BCORL1 (Fig.3). In this section, we will describe frequency, prognostic and functional implication of

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

His goal is to find out how this gene leads to CML in patients, and hopefully, find a way to stop it. The bcr/abl protein constantly tells cells, specially myeloid cells, that it is time to divide, causing uncontrollable replication, and these cells have a mutation in them, they don’t die like normal cells do, causing the body to overflow with these useless cancer cells. Researches at Ciba-Giegy began working on a way to inhibit the bcr/abl tyrosine kinases from signaling to cells. This work resulted in a compound known as STI-571, which was a targeted kinase inhibitor. One of the fears this team faced was, if you inhibit a kinase, do you inhibit them all?

Prof. Jonathan Bramson holds a BSc in Biochemistry and a PhD in Experimental Medicine from McGill University. He has published 96 research manuscripts, 11 review articles, and 2 book chapters. He has also submitted 3 patent applications in the area of immunotherapy. His research is focused on the mechanisms by which the adaptive immune system recognizes and responds to tumours and a specific interest is the development of immunological strategies to fight cancer. He is currently a tenured professor at the department of pathology and molecular medicine at McMaster University, since 2009 director of the McMaster Immunology Research Centre (MIRC) and holder of the John Bienenstock Chair in Molecular Medicine as well as the Tier I Canada Research

Acute Panmyelosis with Myelofibrosis (APMF) is a rare type of acute myeloid leukemia that manifests with a rapidly fibrotic bone marrow and progressive cytopenias. APMF is usually fatal, a consequence of the disease’s ubiquitous pathologic and disease features, rapidly progressive course, and poor response to traditional treatments. The disease is pathologically recognized for its heavily fibrotic marrow, increased overall cellularity, immaturity of all cell line lineages, abnormal megakaryocyte population, and lack of driver mutations that likely contribute to the rapid and progressive disease course. In this chapter, we focus on how the hematologist and pathologist alike can best identify and manage this disease in light of these clinical challenges. We discuss the background of this unique and deadly disease and what led to the identification of this disease from pathologically similar entities. Morphology and recognition of characteristic disease features, including immunophenotypic findings, cytogenetics and morphology are discussed. The identification and distinguishing features of this disease are explored in the setting of a comprehensive differential diagnoses that may mimic this pathologic state. Finally, we address disease prognosis and suggestions on management in light of the limited studies available regarding management.

Chronic Myeloid Leukaemia is a hematopoietic proliferative disorder associated with a specific defect in the gene (Ciesla 2007, pp. 189). The gene defect is caused due to the translocation of the genetic material between chromosome 9 and chromosome 22 (t9: 22). The translocation prompts to the development of a hybrid gene BCR-ALB in the Philadelphia chromosome, or Ph1. Therefore, this fusion gene mutation affects the maturation and differentiation of the haematopoietic cells (Ciesla 2007, pp. 189). However the introduction of a BCR-ALB particular tyrosine kinase inhibitor, Imatinib has significantly enhanced the survival rate of the patient with chronic myeloid leukaemia (Hochhaus, et al.2015). This essay will briefly describe the diagnosis, treatment and future strategies for chronic myeloid leukaemia.

MYC oncoprotein is a transcriptional factor that activates genes involved in cell proliferation and growth. Thus translocations or other gene rearrangements involving MYC may promote cell proliferation and is classically associated with high-grade B-cell lymphomas such as Burkitt lymphoma. MYC rearrangements however, are not unique to Burkitt lymphoma and have been observed in other B-cell lymphoproliferative disorders, including subsets of diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma, blastoid mantle cell lymphoma, plasma cell myeloma, and lymphoblastic lymphoma. Aberrations in MYC have been reported rarely in de novo B-cell prolymphocytic leukemia (B-PLL). In CLL, aberrations of MYC are a very rare (<1 % of CLL)

In vitro: AMG 337 could inhibit MET kinase activity effectively, AMG 337 also showed exquisite selectivity for MET when tested against a diverse panel of over 400 protein and lipid kinases. In addition, AMG 337 was found to inhibit HGF-dependent MET phosphorylation. Furthermore, the treatment with AMG 337 could only affect the viability of two gastric cancer cell lines (SNU-5

The morphology and functions of specialized cells within tissues such as muscle requires the unique organization of the actin cytoskeleton this actin cytoskeleton rely on actin network, vinculin, to locked the filamentous actin (F-actin) to the membrane.1 Vinculin is a structural protein that plays an important role in multiple protein assemblies linking the extracellular matrix to actin cytoskeleton.2 Vinculin is an 116 kDa cytoskeletal protein linked to cell-matrix and cell-cell junctions. It is said to work as one of a few interconnecting proteins required to secure the F-actin to the membrane. Vinculin has a helical head and tail domains attached by a flexible proline-rich linker.3 The head and tail domain mingle in an autoinhibitory manner, blocking binding to a significant number of prospective ligands.4 In addition to vinculin, there is metavinculin (MV), which is a splice variant of vinculin. MV is a muscle-specific splice of vinculin and is expressed in smooth and cardiac muscle tissue. MV is linked to dilated cardiomyopathy (DCM) deficiency which is a form of heart disease.

Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires a series of mutation during mitosis to develop, its characteristics can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells have make it hard to find a single effective treatment for cancer. The focus of research now lies

Carfilzomib, is a second-generation proteasome inhibitor, initially approved by the Food and Drug Administration in 2012, either as a single agent or in combination with other known anti-myeloma treatments in the therapy of relapsed/refractory multiple myeloma (RR-MM). Currently, carfilzomib is also investigated in the de novo setting of

BCR-ABL target mostly common in the growth of Cronic Myelogenous Leukemia. BCR pathway use virus as vitors to target cell that has effect on tumor sequences. If specific sequence is target this can seperate the cancer cells and inhibit cell growth.

Tumor Angiogenesis A distinct subset of PV TAMs has been shown to regulate angiogenesis in various mouse primary tumor models and to correlate with microvessel density in human tumors. BM transplant experiments conducted by De Palma et al. (2003, 2005) identified a subset of BM-derived TAMs that cluster around tumor blood vessels and express higher levels of the angiopoietin receptor, TIE2, and the mannose receptor,

Discuss in detail the effects that an activating mutation in the IKBKB gene would be expected to have on the downstream signalling pathway components and target gene expression, and how these effects are measured in the article.