scholarly journals Plasmacytoma in patients with multiple myeloma: morphology and immunohistochemistry

2020 ◽  
Author(s):  
Maiia Firsova ◽  
Larisa Mendeleeva ◽  
Alla Kovrigina ◽  
Maxim Solovev ◽  
Valery Savchenko
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Bone Destruction ◽  
Extramedullary Plasmacytoma ◽  
Small Sample ◽  
Histological Structure ◽  
Ki 67 ◽  
Mean Values ◽  
Significant Difference ◽  
Tissue Specimens

Abstract Background. To study the histological structure and immunohistochemical (IHC) parameters of the plasmacytoma tumour substrate in patients with multiple myeloma (MM). Methods. The study included 21 patients (10 men/11 women) aged 23 to 73 years old with newly diagnosed MM complicated by plasmacytoma. Bone plasmacytoma was diagnosed in 14 patients, and extramedullary plasmacytoma was diagnosed in 7 patients. Plasmacytoma tissue specimens were examined using a LEICA DM4000B microscope. Anti-CD56, anti-CD166, anti-CXCR4, anti-Ki-67, and anti-c-MYC antibodies were used for IHC study of plasmacytoma biopsies. Results. When comparing the morphology of bone and extramedullary plasmacytoma, no significant differences were revealed; however, the substrate of extramedullary plasmacytoma was more often represented by tumour cells with an immature morphology than was the bone plasmacytoma substrate (57.1% vs. 28.6%, respectively). We revealed a significant difference in the expression of CD166 between bone and extramedullary plasmacytoma. The mean values ​​of CD166 expression in bone plasmacytoma cells were significantly higher (36.29 ± 7.61% versus 9.57 ± 8.46%, respectively; p = 0.033) than those in extramedullary plasmacytoma cells. We noticed that in extramedullary plasmacytoma cells, there were higher values for the Ki-67 index than in bone plasmacytoma cells, and this result was independent of cell morphology. Conclusion. The mechanisms involved in the dissemination of tumour plasma cells are currently unexplored. Even in such a small sample, some differences in expression could be identified, which may indicate that different mechanisms lead to the formation of bone and extramedullary plasmacytomas. Specifically, the expression of CD166 in extramedullary plasmacytoma cells was almost 4 times lower than that in bone plasmacytoma cells, which may indicate the involvement of CD166 in the mechanisms of bone destruction. The proliferative activity of extramedullary plasmacytoma cells was shown to be higher than that of bone plasmacytoma cells.

scholarly journals Plasmacytoma in patients with multiple myeloma: morphology and immunohistochemistry

2019 ◽  
Author(s):  
Maiia Firsova ◽  
Larisa Mendeleeva ◽  
Savchenko Valeri ◽  
Alla Kovrigina ◽  
Maxim Solovev
Keyword(s):  
Plasma Cells ◽  
Bone Destruction ◽  
Extramedullary Plasmacytoma ◽  
Histological Structure ◽  
Ki 67 ◽  
Mean Values ◽  
Significant Difference ◽  
High Proliferative Activity ◽  
The Mean ◽  
Tissue Specimens

Abstract Background. To study the histological structure and immunohistochemical (IHC) parameters of the plasmacytoma tumor substrate in patients with MM. Methods. The study included 21 patients (10 men/11 women) aged 23 to 73 years old with a newly diagnosed MM complicated by plasmacytoma. Bone plasmacytoma was diagnosed in 14 patients, and extramedullary plasmacytoma was diagnosed in 7 patients. Plasmacytoma tissue specimens were examined using a LEICA DM4000B microscope. Anti-CD56, CD166, CXCR4, Ki-67, c-MYC antibody panels were used for the IHC study of plasmacytoma biopsy. Results. When comparing the morphology of bone and extramedullary plasmacytoma, no significant differences were revealed, however, when the substrate of the extramedullary plasmacytoma was compared to the bone plasmacytoma substrate it was more often represented by tumor cells with immature morphology (57.1% vs. 28.6%). We founded a significant difference in the expression of CD166 in bone and extramedullary plasmacytoma. It was shown that the mean values ​​of the CD166 expression in bone plasmacytoma cells were significantly higher (p = 0.033) and amounted to 36.29 ± 7.61% versus 9.57 ± 8.46% in extramedullary plasmacytoma cells. We noticed that in the cells of the extramedullary plasmacytoma, there were higher values ​​in the Ki-67 index than observed in comparison to the cells of the bone plasmacytoma independent of the cells’morphology. Conclusion. The mechanisms involved in the dissemination of tumor plasma cells are currently unexplored. Our study revealed significant differences in the IHC parameters of the tumor substrate from extramedullary and bone plasmacytoma. Thus, the expression of the CD166 in extramedullary plasmacytoma cells is almost 4 times lower than that in bone plasmacytoma cells, which may indicate the involvement of CD166 in the mechanisms of bone destruction. A high proliferative activity of extramedullary plasmacytoma cells was shown when compared to bone plasmacytoma cells.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

scholarly journals Current approaches to supportive care in multiple myeloma

2011 ◽  
Vol 139 (suppl. 2) ◽  
pp. 123-128
Author(s):  
Nenad Govedarovic ◽  
Tomislav Vukicevic
Keyword(s):  
Multiple Myeloma ◽  
Chronic Condition ◽  
Malignant Disease ◽  
Plasma Cells ◽  
Supportive Therapy ◽  
Bone Destruction ◽  
Monoclonal Protein ◽  
Blood Disease ◽  
Skeletal Disease

Myeloma multiplex is a malignant blood disease in which monoclonal expansion of malignant plasma cells occurs, together with hyperproduction of monoclonal protein,as well as impairment of normal haematopoiesis. Specific features of myeloma include bone destruction, renal failure and immunologic deficiency which decreases the overall quality of the patient?s life. Thus, prevention and supportive therapy of skeletal disease, anaemia, pain, nausea, infection and hypercalcemia, represent the essential part of therapy in myeloma patients. Improvements achieved in the specific haematological treatment, including supportive measures of complications of multiple myeloma, previously defined as incurable malignant disease, results in the improvement of the overall survival and the quality of life of these patients, thus qualifing multiple myeloma into a chronic condition.

scholarly journals Pulsatile Midline Solitary Plasmacytoma in the Frontal Head Region-A Case Report”

2016 ◽  
Vol 32 (1) ◽  
pp. 39-42
Author(s):  
Md Atikur Rahman ◽  
Aklaque Hossain Khan ◽  
Kanak Kanti Barua
Keyword(s):  
Multiple Myeloma ◽  
Differential Diagnosis ◽  
Case Report ◽  
Histological Examination ◽  
Plasma Cells ◽  
Extramedullary Plasmacytoma ◽  
Solitary Plasmacytoma ◽  
Rare Entity ◽  
Head Region ◽  
Malignant Plasma Cell

Primary craniocerebral plasmacytomas are uncommon and represent only 0.7 % of all plasmacytomas. In this case solitary plasmacytoma in the midline frontal head region of the skull and discuss the clinical features and prognosis of this tumor. Plasmacytoma can present as multiple myeloma, solitary plasmacytoma of the bone or extramedullary plasmacytoma. Solitary plasmacytoma is a rare entity that composes of malignant plasma cells and involves the bone to form only one or two lesions without evidence of disease dissemination. It accounts for only 4% of malignant plasma cell tumors. 50 years old male was suffering from plasmacytoma in the frontal head region in our case which is pulsatile. On images showed multiple differential diagnosis but after operation histological examination revealed plasmacytoma. Bangladesh Journal of Neuroscience 2016; Vol. 32 (1): 39-42

scholarly journals PC3 - 216 Presentation of Intradural Extramedullary Plasmacytoma with Intratumoral Hemorrhage: Case Report and Review of Literature

2016 ◽  
Vol 43 (S4) ◽  
pp. S22-S22
Author(s):  
A. Ghare ◽  
F. Haji ◽  
K. MacDougall
Keyword(s):  
Multiple Myeloma ◽  
Differential Diagnosis ◽  
Plasma Cells ◽  
Extramedullary Plasmacytoma ◽  
Left Frontal Lobe ◽  
Axial Mass ◽  
Dural Tail ◽  
History Of ◽  
Intradural Extramedullary ◽  
Contrast Ct

Plasmacytomas are solitary tumours characterized by neoplastic proliferation of plasma cells and can be found isolated or in associated with multiple myeloma. Plasmacytomas uncommonly occur intracranially, and dural plasmacytomas without involvement of the calvarium are exceedingly rare. Reported cases indicate durally-based plasmacytomas mimick the appearance of meningioma, lymphoma or sarcoma of the dura. The authors report a case of a 77-year-old male with known multiple myeloma who presented with a 3-week history of confusion, speech impediment, and right sided weakness. A non-contrast CT scan revealed a dense extra-axial mass in the left frontal lobe with initial concerns of an extra-axial hemorrhage. A subsequent MRI demonstrated a contrast enhancing mass with a broad-based dural tail and no underlying calvarial lesion. Differential diagnosis included meningioma or intracranial plasmacytoma. The patient underwent surgical resection and was found to have intratumoural hemorrhage, with pathology confirming plasmacytoma. In the published literature, there are only 20 prior reports of dural plasmacytomas (with and without primary calvarial infiltration), of which only five previous cases reported associated intratumoural hemorrhage. Our case, along with this literature, suggests that new onset of focal neurologic deficits in patients with a history of multiple myeloma merits careful investigation, and that intracranial plasmacytoma should be considered on the differential diagnosis even when imaging reveals masses consistent with hemorrhage or meningioma.

scholarly journals MULTIPLE MYELOMA AS A FORM OF LEUKEMIA

Blood ◽  
1949 ◽  
Vol 4 (9) ◽  
pp. 1049-1067 ◽  
Author(s):  
MICHAEL A. RUBINSTEIN
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Bone Destruction ◽  
Tumor Formation ◽  
Diffuse Infiltration ◽  
Skeletal Involvement ◽  
The Difference ◽  
Distinguishing Features ◽  
Osseous System

Abstract The conventional points in the differential diagnosis between myeloma and leukemia have been discussed. Evidence has been brought to show that these points of distinction cannot be regarded as being of fundamental nature. Instances are abstracted where cases of multiple myeloma show the various characteristics of leukemia and vice versa. 1. Leukemic features in myeloma have been shown in: a. diffuse infiltration in multiple myeloma without circumscribed tumor formation and without any gross bone destruction; b. extraskeletal visceral myelomatous spread involving the kidney, spleen, lymph nodes, etc.; c. invasion of peripheral blood in myeloma—occasional myeloma cells (corresponding to the aleukemic forms of leukemia) may frequently be found in concentrated smears, even though they may be missed on routine examination; however, massive invasion of peripheral blood is rare; d. increased uric acid content of the blood and elevated basal metabolism, characteristic of leukemia, frequently seen also in myeloma; e. occurrence of myeloma in youth; f. symptomatology of multiple myeloma at times not referable to the osseous system. 2. Myeloma features in leukemia have been shown in: a. skeletal involvement in leukemia; b. very rare medullary forms of leukemia (without visceral involvement); c. occurrence of Bence-Jones proteinuria or d. hyperproteinemia with hyperglobulinemia in rare cases of leukemia; e. instances when the symptomatology of leukemia was referable to the osseous system. 3. Coexistence of multiple myeloma and leukemia is reviewed from the literature, and a case is reported of extensive mixed lymphocytic and plasma cell infiltration. In conclusion, the difference between myeloma and leukemia, as far as the listed conventional distinguishing features are concerned, is merely one of incidence: what is rare in one disease, is common in the other, and vice versa. Multiple myeloma is in all probability a leukemia of plasma cells.

Dose Intensive Induction Chemotherapy Does Not Decrease Tumor Contamination of Autograft or Improve Survival for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2932-2932
Author(s):  
Farzana A. Sayani ◽  
Nizar J. Bahlis ◽  
Peter Faris ◽  
Mary Lynn Savoie ◽  
Ahsan Chaudhry ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Small Sample ◽  
Cell Transplant ◽  
Intensive Chemotherapy ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Time To Relapse

Abstract Multiple dose intensive chemotherapy regimens have been used for induction/mobilization of stem cells for autologous stem cell transplantation (ASCT) in multiple myeloma. However, the exact role and regimens of such dose intensive chemotherapy has not been clearly defined. We therefore did a retrospective study to determine if dose intensive cyclophosphamide (Cyclo) 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in improved relapse rate and survival compared to standard mobilization with only Cyclo 2 g/m2. Between January 1998 and March 2004, a consecutive series of 57 newly diagnosed multiple myeloma patients receiving DICEP (38) or Cyclo (19) for in-vivo purging/mobilization were analyzed. Both groups were similar in regards to age and sex. There were no significant differences in IPI score, Durie-Salmon stage, B2 microglobulin, calcium, creatinine and albumin levels between treatment groups. Outcomes included time to relapse and time to death. Median follow up time was 799 days. Kaplan-Meier plots for time to relapse showed no significant difference (p=0.0992). Median relapse time in the DICEP group was 905 days (95% CI 580–1604) compared to 1112 days (95% CI 742-infinity) in the Cyclo group. Kaplan-Meier plots for overall survival showed no significant difference between both groups (p=0.8664). The median survival times have not yet been reached in either group and are not reported. Analysis revealed no discernable confounding risk factors. Effects of treatment on outcomes were not altered after adjusting for IPI score and Durie-Salmon staging using the stratified log-rank test. Small sample size and short duration of followup are potential limiting factors for this study, however, preliminary analysis of a larger sample of 91 multiple myeloma patients receiving either DICEP or a less intense induction/mobilization regimen, also revealed no significant difference in disease free or overall survival. Monoclonal plasma cell contamination of stem cell products was not significantly different between both groups (DICEP 42.9%, Cyclo 56.3%, p=0.5573). This study therefore suggests that the very intense DICEP induction/mobilization regimen results in no significant difference in survival outcomes. The more intense regimen does not significantly decrease tumor contamination of autograft stem cells. Overall, our experience suggests that novel induction therapies such as bortezomib, lenolidomide etc. should be pursued in preference to any further study of high dose cytotoxic chemotherapy induction. Figure Figure

Clonal and Subclonal Cytogenetic Aberrations: Association with D-Type Cyclin Expression and Event-Free Survival (EFS) in Multiple Myeloma (MM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3439-3439
Author(s):  
Dirk Hose ◽  
John DeVos ◽  
Nadine Müller ◽  
Jean-Francois Rossi ◽  
Christiane Heiß ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Western Blotting ◽  
Plasma Cells ◽  
Early Event ◽  
Expression Data ◽  
Rt Pcr ◽  
Qrt Pcr ◽  
Cytogenetic Aberrations ◽  
Significant Difference

Abstract AIM. Expression changes of D-type cyclins are thought to be an early event in the genesis of Multiple Myeloma and are associated with distinct cytogenetic aberrations. These aberrations appear with different percentages (“clonal” or “subclonal”) in a given patient. We assessed whether the height of CCND expression assessed by gene expression profiling and quantitative RT-PCR (qRT-PCR) correlates with the presence of clonal or subclonal aberrations of 11q13, t(11;14) and t(4;14). PATIENTS AND METHODS. 128 newly diagnosed MM-patients (65 training (TG)/63 independent validation group (VG)) and 14 normal donors (ND) were included. Bone marrow aspirates were CD138-purified by activated magnetic cell sorting. RNA was in-vitro transcribed and hybridised to Affymetrix HG U133 A+B GeneChip (TG) and HG U133 2.0 plus array (VG). CCND1 and CCND2 expression was verified by real time RT-PCR and western blotting. iFISH was performed on purified MM-cells using probesets for chromosomes 1q21, 9q34, 11q23, 11q13, 13q14, 15q22, 17p13, 19q13, 22q11 and the translocations t(4;14) and t(11;14). Clonal aberrations were defined as being present in >60%, subclonal aberrations in 20 to 60% of MMC in a given patient. Expression data were gcrma normalised and a Kruskal-Wallis rank sum test used (Bioconductor). RESULTS. 11q13+. CCND1 (208711_s_at, 208712_at) is significantly higher (p<0.0001), CCND2 (200953_s_at, 200951_s_at) significantly lower (p<0.0001) expressed in MMC harbouring clonal, compared to subclonal, or no gain of 11q13. t(11;14). CCND1 is significantly higher (p<0.0001), CCND2 significantly lower (p<0.0001) expressed in MMC harbouring clonal, compared to subclonal, or no t(11;14). t(4;14). CCND1 is significantly lower (p<0.0001), CCND2 significantly higher (p<0.0001) expressed in MMC harbouring clonal compared to subclonal, or no t(4;14). The expression of CCND3 (201700_at) is not significantly different between the 3 groups for all aberrations investigated. CCND2 and CCND3, but not CCND1 are expressed by normal plasma cells. Results have been verified by qRT-PCR (n=40) for CCND1 and CCND2. Expression of CCND1, CCND2 and CCND3 has been verified by western blotting on selected samples. The expression of CCND2 correlates with short EFS, but not if patients with t(4;14) are excluded. There is no significant difference in EFS for patients harbouring the respective aberrations in a clonal or subclonal pattern. CONCLUSION. An additional copy of 11q13 or t(11;14) correlates with increased CCND1 and decreased CCND2 expression, a t(4;14) is associated with an increase of CCND2 and a decrease of CCND1 expression. In each case, the height of the CCND-expression is significantly different whether the respective aberration is clonal or subclonal. Thus, when interpreting expression data in the context of cytogenetic aberrations, it is important to consider if plasma cells carry a respective aberration in a subclonal/clonal pattern.

Evaluation of NCAM and DKK1 Expression in Multiple Myeloma and MGUS by Gene and Tissue Microarrays: Expression Accompanies Progression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3399-3399
Author(s):  
Sushil Gupta ◽  
Yongsheng Huang ◽  
James Stewart ◽  
Fenghuang Zhan ◽  
Bart Barlogie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Plasma Cells ◽  
Molecular Classification ◽  
Tissue Microarrays ◽  
Bone Lesions ◽  
Bone Marrow Biopsies ◽  
Dkk1 Expression ◽  
Significant Difference ◽  
Expression Microarrays

Abstract Introduction: Expression NCAM1, a cell adhesion molecule involved in neuron-neuron adhesion, is also expressed by multiple myeloma (MM PC). Osteolytic bone lesions are a hallmark of MM and elevated expression of NCAM in MM PC has been correlated with this process (Ely and Knowles, 2003). We have previously reported that MM PC express DKK1 and MM blocks osteoblast differentiation in a DKK1-specific manner, suggesting that secretion of the Wnt signaling inhibitor plays a role in MM bone disease. Herein we used gene expression microarrays and tissue microarrays (TMAs) to investigate the simultaneous expression of DKK1 and NCAM in MM and MGUS. Methods: The study population consisted of 198 newly diagnosed MM and 44 MGUS. RNA from CD138-selected plasma cells was hybridized to Affymetrix U133Plus microarrays and data processed with Affymetrix Microarray Suite GCOS1.1 software. TMAs were constructed from formalin-fixed, paraffin embedded bone marrow biopsies. Serial sections of TMA were immunostained for CD138, NCAM and DKK1. TMAs were scanned using ScanScope using 20x lens, assessed using TMA lab software (Aperio Technologies) and scored as an average number of cells in the context of CD138 staining. Results: When put in context of a recently described molecular classification (Zhan et al., 2006), NCAM and DKK1 were found significantly co-over-expressed (DKK1+/NCAM+) in HYPERDIPLOID MM (P < 0.01); NCAM+/DKK1− was typical for MMSET-spike MM (P<0.001); NCAM−/DKK1+ DKK1 was characteristic of MM in MAF-spike disease (P < 0.001), CCND1 spikes with co-expression of CD20 (P<0.01), and the so-called MYELOID subgroup (P<0.001). In contrast, virtually all cases of MGUS were DKK1−/NCAM-. On TMAs, DKK1 expression varied in CD138-positive cells in MM, and in osteocytes and megakaryocytes in MM and MGUS, but was clearly negative in osteoblasts/lining cells. NCAM expression, was also variably expressed in PC of MM cases and in virtually 100% of osteoblasts/lining cells in both MM and MGUS. Osteocytes were distinctly negative for NCAM in both diseases. Of 195 analyzable MM biopsies, PC were DKK1+ in 1% to > 90% of PC in 191 (98%); of these, 94 were also NCAM+ in 5% to > 90% of PC; 1 case was positive for NCAM+/DKK− and 3 were NCAM−/DKK−. There was no significant difference in clinical parameters and survival in a comparison of NCAM+/DKK+ and NCAM−/DKK+ groups. DKK1 gene expression was higher in DKK1+/NCAM+ than in DKK1+/NCAM− MM (P=0.006); NCAM gene expression was higher in DKK1+/NCAM+ than in DKK+/NCAM− MM (P<0.0001) and NCAM was the number one SAM-defined gene over-expressed in DKK1+/NCAM+ relative to DKK1+/NCAM− disease. Consistent with GEP data, DKK1+/NCAM+ MM was over-represented in HYPERDIPLOID MM (32% v. 10%; P<0.001), while DKK1+/NCAM− disease was overrepresented in MAF-spike (15% v. 2%; P=0.003) and MYELOID subgroups (32% v. 18%; P=0.03). DKK1+/NCAM+ MM was completely absent in CCND1-spike /CD20-negative disease, with only 4% of DKK1+/NCAM− cases in this subgroup. No difference was observed for the other subtypes. Conclusion: DKK1 is expressed in all cases of MM with half also expressing NCAM. Neither gene is expressed in MGUS PC. These data suggests that expression of these genes in plasma cells accompanies disease progression.

A Potential Biomarker Panel of Multiple Myeloma Identified Using Label-Free Mass Spectrometry-Based Quantitative Proteomics

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2890-2890
Author(s):  
Attaya Suvannasankha ◽  
Colin D. Crean ◽  
Heather M. Sahm ◽  
Rafat Abonour ◽  
Sherif Farag ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Protein Expression ◽  
Plasma Cells ◽  
Expression Profiles ◽  
Peptide Identification ◽  
Clinical Samples ◽  
Normal Plasma ◽  
Potential Biomarker ◽  
Significant Difference

Abstract Abstract 2890 Background: Multiple myeloma is an incurable and fatal hematologic malignancy. Recent gene microarray studies showed distinct gene expression profiles defining MM subgroups and their association with cytogenetic abnormalities and treatment outcome. However, aside from transcriptional control, a variety of post-transcriptional/post-translational modifications likely play an important role in regulating protein expression and function, and ultimately may prove informative for predicting tumor behavior. Objectives: We hypothesize that the protein profile in MM cells is different than normal plasma cells. Methodology: Normal plasma cells and myeloma cells were isolated using CD138 immune magnetic beads from bone marrow aspirates from healthy volunteers or patients with newly diagnosed MM, respectively. CD138+ cells were frozen and subsequently analyzed in one batch. Proteins were digested by trypsin. Tryptic peptides were injected onto an HPLC system and analyzed on a Thermo-Fisher LTQ mass spectrometer. Peptide identification and quantification were carried out using proprietary algorithms. Identified proteins were categorized into priority groups based on the quality of the peptide identification by tandem mass spectrometry. Proteins with significant changes in expression level were further analyzed by bioinformatics tools for the determination of the biological significance. Results: In the discovery phase of this study, 433 proteins were identified and their expression levels were quantitatively compared. 169 of these proteins demonstrated a significant difference between normal plasma cells and MM cells. Among the significantly changed proteins, 18 were identified and quantified with high confidence, and were therefore chosen for further validation. The identified proteins are known to be involved in the glycolysis/gluconeogenesis pathway, the oxidative phosphorylation pathway, cysteine metabolism and the pentose phosphate pathway. None of these proteins are known to be of prognostic value or being currently targeted for therapy in MM. A high-throughput LC/MS-based multiple-reaction-monitoring (MRM) assay for quantitative validation of these candidates with clinical samples is ongoing. To date, using the MRM assay, we were able to detect MRM peptides for 13 of the 18 targeted proteins in clinical samples. The quantification of these peptides will be further confirmed using a separate set of clinical samples. Conclusion: Significant differences in protein expression were observed between MM and normal plasma cells. The study presents an important step toward using proteomics as a tool to develop diagnostic and/or prognostic biomarkers in the clinical setting. However, both follow-up analytical and clinical validations are required before they can serve as disease-specific biomarkers. Disclosures: Abonour: Celgene: Membership on an entity's Board of Directors or advisory committees.

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