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Historically, lymphomas have been defined by their histologic or morphologic features.
We have recently learned, however, that the biology is also important in several ways: Disease biology might predict response to treatment, and it has the potential to impact treatment decision-making.
The starting point in a discussion about genetics in aggressive B-cell lymphoma is the observation that some patients can be cured and others cannot.
Studies have investigated the biologic underpinnings for these different outcomes. A pioneering genetic evaluation of diffuse large B-cell lymphoma DLBCLpublished by Alizadeh and colleagues inshowed 2 subtypes: The name germinal-center DLBCL was chosen because the gene expression of this profile more closely fits with the normal germinal center—derived B cell.
In the subtype non—germinal center DLBCL, or activated B-cell lymphoma, the gene expression profiling more closely fits a normal activated B cell. This distinction is important because better outcomes are seen in patients with the germinal-center subtype than with Aggressive drivers non—germinal-center subtype.
This insight from 15 years ago has led to recent trials that are specifically powered to test new treatments in one genetic subtype vs the other. We are hopefully very close to understanding whether these 2 subtypes of DLBCL should be treated differently. Approximately 10 years ago, it became clear that the t 8;14 translocation was also seen in DLBCL, as well as in another type of lymphoma that shares morphologic features of both DLBCL and Burkitt lymphoma.
This phenotype is very proliferative and drug-resistant, and it is associated with a poor prognosis. Both double-hit and triple-hit lymphomas have a poor prognosis with standard treatment.
Few patients with double-hit lymphoma are cured with this approach. Currently, the best treatment for double-hit lymphoma is unknown. There are retrospective reviews suggesting that a more intensive therapy, such as etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab EPOCH-Rmay be better than standard treatment.
Prospective trials are underway. An additional challenge is that we do not know the clinical significance of genes that are amplified or duplicated but not rearranged. The most common example is the presence of 2 or 3 extra copies of MYC. Currently, that profile is not considered double-hit lymphoma, and there are no clear treatment guidelines.
SS Immunohistochemical staining to identify protein expression of MYC also showed that there are lymphomas in which MYC and BCL2 genes are overexpressed at a protein level, without the genetic rearrangements. The cut points to define overexpression vary from study to study.
As shown in a study by Hu and colleagues, patients with double-expressor DLBCL have worse outcomes than patients in whom these proteins are not overexpressed; in general, only one-third of patients have long-term disease control with R-CHOP.
SS Double-hit lymphoma and double-expressor lymphoma are probably related, but are different categories. Patients who have the double-hit rearrangement usually have protein overexpression, and therefore have the double-expressor phenotype.
However, the converse is not always true: SS The double-hit lymphomas can be detected with fluorescence in situ hybridization FISH or standard cytogenetic analysis. The double-expressor lymphomas are diagnosed by immunohistochemistry.
However, gene-expression profiling is not routinely available nor is it considered a standard test. A new parsimonious digital gene-expression assay Lymph2Cx; NanoStringwhich is being tested in clinical trials but is also available commercially, looks at 20 genes to help determine cell of origin.
Categorization now involves both morphology and genetics.Each year millions of cellular telephone calls regarding roadside emergencies and life-threatening accidents pour into New Jersey's emergency call centers. What is Aggressive Driving?
Aggressive driving can refer to any display of aggression by a driver, tailgating, flashing headlights, speeding or weaving through traffic are just some forms of aggressive driving.
Through all this we’ve gotten an earful about what we’ve come to call the shadow side of Minnesota Nice. Take Pam, a transplant from Colorado.
Mar 08, · Watching super aggressive drivers go head to head is HILARIOUS, but dangerous. Riding around, watching idiots do their thing.
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Instead, it sharpens the most important safety equipment of all: the mind of the driver. Uber driver pay conclusions on How much do Uber drivers make in ?
Driving for Uber pays very well compared to other jobs with similar experience requirements (which is literally none) and offers a lot of freedom and independence.