Articles tagged with: Chromosomal Abnormalities
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German researchers recently reported that certain chromosomal abnormalities in patients' myeloma cells are associated with more rapid progression from smoldering myeloma to active, or symptomatic, multiple myeloma.
Specifically, patients in the study who had the chromosomal abnormalities del(17p), t(4;14), and 1q gain, as well as patients with more chromosomes than normal (hyperdiploidy), experienced shorter times until progression to symptomatic myeloma.
Previous studies have shown that hyperdiploidy positively affects outcomes for patients with symptomatic myeloma. In this study, however, the investigators found that hyperdiploidy negatively affects outcomes for smoldering myeloma patients.
The researchers …
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Findings from a recent retrospective study conducted at the Mayo Clinic indicate that chromosomal abnormalities may influence which symptoms a multiple myeloma patient has at diagnosis.
For instance, the researchers found that newly diagnosed myeloma patients with the chromosome 14 translocation t(14;16) are more likely to have kidney damage, while patients with extra chromosomes are more likely to have bone disease or anemia.
They also found that patients with t(14;16) who did not have kidney damage survived significantly longer (a median of 44 months) compared to those with kidney damage (9 months). …
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An international panel of multiple myeloma experts, known as the International Myeloma Working Group (IMWG), recently released a consensus statement on risk stratification for patients with multiple myeloma.
Risk stratification refers to the classification of patients into different categories based on likely disease outcome.
The new IMWG risk stratification, for example, has three risk categories: low-risk, standard-risk, and high-risk.
In the new system, determination of a patient's risk classification is based on three factors: a patient's disease stage according to the International Staging System (ISS); the presence of certain chromosomal abnormalities in …
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Alcohol Consumption May Reduce Risk Of Developing Myeloma – Results from a recent retrospective study suggest that alcohol consumption may be associated with a reduced risk of multiple myeloma. The researchers analyzed data from 1,567 myeloma patients and 7,296 healthy individuals from a number of treatment centers across the world that are part of the International Multiple Myeloma Consortium. Their findings show that people who ever drank alcohol had a lower risk of multiple myeloma compared to those who never drank. This association was true for all types of alcoholic beverages (beer, wine, and liquor) that the researchers examined. However, the researchers did not find any relationship between the frequency of alcohol consumption or cumulative intake of alcohol and the rate of myeloma. The investigators note that this is the largest investigation so far of the relationship between alcohol consumption and multiple myeloma. However, they caution that their findings need to be confirmed by prospective studies. For more information, please see the study in Cancer Epidemiology, Biomarkers & Prevention (abstract).
Deletions In Chromosome 1 Linked To Poor Multiple Myeloma Prognosis – French researchers have linked deletions in specific regions of chromosome 1, called 1p22 (15 percent of myeloma patients) and 1p32 (7 percent), to poor myeloma prognosis. Compared to patients without either deletion, patients with the deletions showed shorter progression-free survival (19.8 months with 1p22 deletion and 14.4 months with 1p32 deletion versus 33.6 months without either deletion) and shorter overall survival (44.2 months with 1p22 deletion and 26.7 months with 1p32 deletion versus 96.8 months without either deletion). Based on the dramatic of impact of the 1p32 deletion on survival, the researchers recommend that all myeloma patients be tested for it at diagnosis. The French investigators used a technique called fluorescence in situ hybridization (FISH) to detect 1p22 and 1p32 deletions in samples from 1,195 myeloma patients under the age of 66 years. About two thirds of the study participants received induction therapy with the older chemotherapy combination regimen of vincristine (Oncovin), doxorubicin (Adriamycin), and dexamethasone (Decadron), while the other third received induction therapy with a Velcade (bortezomib)-based regimen. After their induction therapy, all patients underwent autologous stem cell transplantation with high-dose melphalan (Alkeran). The negative impact of the chromosome 1 deletions was seen regardless of a patient's induction regimen. For further information, please see the study in Leukemia (abstract).
Researchers Identify Genetic Variations Associated With Increased Risk Of Multiple Myeloma – British and German researchers recently identified four specific chromosomal regions that differ significantly between multiple myeloma patients and healthy individuals. These regions are present on chromosomes 3, 6, 17, and 22, and denoted as 3q26.2, 6p21.33, 17p11.2, and 22q13.1, respectively. The investigators note that the 3q26.2 region is associated with a gene called TERC (telomerase RNA component) that regulates the length of chromosomes and the aging of cells. Genetic variations of this gene allow cancer cells to avoid the aging process and continue to divide. The findings are based on a comparison of the genetic make-up of 4,692 myeloma patients and 10,990 healthy individuals. This British-German research group previously identified three other genetic regions linked to increased risk for myeloma (see related Beacon news). In the future, the group's findings could lead to tests that determine a person's risk of developing myeloma, and to the development of new treatments for the disease. For more information, please see the press release from the Institute of Cancer Research in the United Kingdom and the study in Nature Genetics (abstract).
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Study Reveals Variations In Minimal Residual Disease Testing For Myeloma – Results from a recent study suggest that testing for residual multiple myeloma after treatment varies widely across medical institutions in the United States. Among 26 institutions surveyed, 42 percent offered testing services for minimal residual disease (MRD). In addition, the tests conducted by some institutions were 100-fold more sensitive than others at detecting residual cells. The parameters used to identify myeloma cells and the number of myeloma cells needed to classify a sample as MRD-positive also varied across institutions. According to the investigators, these findings highlight the need for collaborative efforts to develop standardized criteria for MRD testing. They added that future studies are also required to identify the best time to test for residual disease. Myeloma cells that remain in the bone marrow after treatment contribute to residual disease. Detecting residual disease is thought to be important since previous studies have linked residual disease to shorter survival. MRD testing is performed on bone marrow cells, typically using a technique called flow cytometry. Most of the institutions in this study tested for MRD upon achievement of a complete response. For more information, please see the study in the journal Blood (subscription required).
Blood Levels Of BAFF Protein Linked To Myeloma Disease Activity – Findings from a recent Greek study suggest that blood levels of the protein BAFF can be used as a marker of disease activity in multiple myeloma patients. B cell activating factor (BAFF) plays a critical role in the proliferation of plasma cells. Comparing blood samples from 54 newly diagnosed myeloma patients and 24 healthy individuals, the researchers found that BAFF levels were significantly increased in myeloma patients. Patients with advanced myeloma showed higher BAFF levels than patients with early stage disease. The researchers also measured the concentrations of a number of proteins involved in plasma cell proliferation (including interleukin-6 and interleukin-10) and found that BAFF levels closely paralleled the levels of these proteins. The investigators further measured BAFF concentrations in a subset of patients after they achieved a complete response or very good partial response with chemotherapy. These results showed that BAFF levels were significantly decreased after effective treatment. Based on these findings, the researchers suggest that levels of BAFF in the blood can be used as a marker for myeloma cell proliferation and disease activity. For more information, please see the study in BioMed Research International.
Presence Of Protein CD20 May Predict Disease Outcome In Myeloma Patients With Chromosomal Abnormality t(11;14) – Chinese researchers have recently found that myeloma patients with the chromosomal abnormality t(11;14) may show normal or poor disease outcome depending upon the presence of a protein called CD20. After Velcade (bortezomib)-based treatment, patients whose myeloma cells contained both t(11;14) and the CD20 protein showed significantly longer progression-free survival than patients who had t(11;14) without CD20 (43 months versus 11 months). Overall survival was also longer in patients whose myeloma cells had CD20 as compared to patients without CD20 (54 months versus 17 months). Although t(11;14) is the most common chromosomal abnormality seen in myeloma cells, its impact on treatment outcome has remained controversial (see related Beacon news). In general, patients with t(11;14) are not classified as having high-risk disease. As a caveat, findings from this China-based study may not be directly applicable to myeloma patients of other ethnicities and will therefore require further validation. For more information, please see the study in Leukemia Research (abstract).
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Ratio Of Interleukin Proteins Linked To Progression-Free Survival In Myeloma Patients – Chinese researchers have recently found that a higher ratio of the proteins IL-27 to IL-17 in the bone marrow of multiple myeloma patients may be associated with longer progression-free survival. IL-27 and IL-17 belong to a class of proteins known as interleukins that are produced by immune cells. Interleukins play an important role in orchestrating immune responses against microbes and cancer cells. In the current study, the researchers measured the levels of these proteins in bone marrow and blood samples from myeloma patients and healthy individuals. They found that the ratio of IL-27 to IL-17 was significantly lower in the bone marrow of newly diagnosed myeloma patients, compared to healthy counterparts. Further analysis showed that, among myeloma patients, an increased ratio of IL-27 to IL-17 in the bone marrow was associated with longer progression-free survival. For more information, please see the study in Leukemia Research (abstract).
New Measure Of Chromosomal Instability May Be A Prognostic Tool For Myeloma – In a recent study, researchers from Singapore show that a new measure of chromosomal instability that takes into account both deletions and extra copies of chromosomal regions may be a useful prognostic tool in multiple myeloma. Chromosomal abnormalities, such as changes in the numbers or structure of chromosomes (genetic material), are often seen in myeloma cells. The researchers used data from more than 1,000 newly diagnosed myeloma patients who had received stem cell transplants and patients with relapsed disease who had been treated with Velcade (bortezomib). An analysis of these data showed that patients with a higher value of chromosomal instability showed poorer survival. For more information, please see the study in PLoS ONE.
Erythropoietin May Promote Blood Vessel Formation In Myeloma Patients – Results from a recent Italian study suggest that treatment of multiple myeloma patients with erythropoietin stimulates macrophages to promote blood vessel formation. This effect of erythropoietin could be detrimental to myeloma patients, since growth of blood vessels often strengthens cancer cells by providing better access to nutrients. Erythropoietin is a hormone produced by the kidneys that promotes the generation of red blood cells. Many myeloma patients suffer from anemia (low red blood cell counts) and are treated with erythropoietin. In the Italian study, the researchers found that erythropoietin also affects a type of immune cell called macrophages. Their results show that erythropoietin stimulates macrophages to produce a number of factors that promote blood vessel formation. Macrophages from myeloma patients were also more sensitive to erythropoietin as compared to macrophages from patients with the myeloma precursor monoclonal gammopathy of undetermined significance. For more information, please see the study in Angiogenesis (abstract).
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French researchers recently determined that the chromosomal abnormalities t(4;14) and del(13) are less common in older newly diagnosed myeloma patients than in younger patients.
In contrast, the del(17p) abnormality was found to occur with a similar frequency across myeloma patients of all ages.
The researchers also found that the t(4;14) and del(17p) abnormalities have the same prognostic value in older patients as in younger patients.
Specifically, older patients with t(4;14) and del(17p) had shorter progression-free and overall survival compared to patients without those chromosomal abnormalities.
The del(13) abnormality, on the other hand, …
