Prognostic Significance of BCL-2 Expression in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4840-4840
Author(s):  
Mehmood Hashmi ◽  
Kiarash Kojouri ◽  
Jian Yang ◽  
Sunil Patel ◽  
Mohammad Khan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Median Survival ◽  
Small Sample Size ◽  
Prognostic Significance ◽  
Chemotherapeutic Agents ◽  
Small Sample ◽  
Rank Test ◽  
Number Of Patients

Abstract Background: multiple myeloma (MM) remains an incurable disease that accounts for approximately 10% of all hematologic cancers. Patients (pts) with MM treated with conventional chemotherapy have a median overall survival of 36–42 months. Various adverse prognostic factors have been described in MM, including elevated B2 microglobulin, hypoalbuminemia, cytogenetic abnormalities of chromosome 13 (13q14 del, monosomy 13), and elevated CRP among others. BCL-2 mediates anti-apoptotic pathways and its expression has been implicated with lack of response to certain chemotherapeutic agents and unfavorable prognosis in different human malignancies. Objective: to evaluate the prognostic significance of BCL-2 expression in patients with MM. Methods: adult pts who were diagnosed with MM at our institution since 1/1/90 were retrospectively analyzed. Expression of BCL-2 was determined by immunohistochemistry (IHC) staining of deparafinized bone marrow specimens. Median survival was calculated for BCL-2 (+) and BCL-2 (−) groups. Survival curves were estimated according to the Kaplan-Meier method, and were compared with the use of the log-rank test. Median survivals were also compared by using Wilcoxon-Mann-Whitney test. Two-tailed alpha level of 0.05 was considered statistically significant. SAS® software (Cary, NC) was used for statistical analysis. Results: sixty-six patients were initially identified. Forty-four pts were excluded because bone marrow samples were not available for IHC staining. Twenty-two pts (11 males, 11 females), with a median age at the time of diagnosis of 64 years (range: 46 to 83 years) were included for this analysis. Fourteen pts (64%) had positive BCL-2 bone marrow specimens, including 4 mild, 3 moderate, and 7 strong staining, while for 8 pts (36%), bone marrow specimens did not stain for BCL-2. Twelve pts (86%) from BCL-2 (+) group and 4 pts (50%) from BCL-2 (−) group died during the period of follow-up; 8 pts are still alive at the time of this analysis, 23 to 71 months (median: 39 months) after diagnosis. The median survival among BCL-2 (+) pts was 35 months (95% CI: 24 – 69 months) and among BCL-2 (−) pts was 47 months (95% CI: 13 months - N/A). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8256 and 0.7072, respectively). Conclusion: although our study did not show correlation between BCL-2 expression and overall survival, median survival among BCL-2 (−) pts with MM was 34% longer than BCL-2 (+) pts. The authors recognize the limitations associated with this analysis including the retrospective nature of the study, small sample size, and exclusion of a large number of patients. This study highlights the need for prospective evaluation of the prognostic significance of BCL-2 expression among pts with MM.

scholarly journals Discrepancy of Blast Percentage between the Bone Marrow Aspirate and Flow Cytometry and Its Impact on Survival Outcomes in Patients with Myelodysplastic Syndromes Excess Blast (MDS-EB)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5441-5441
Author(s):  
Meera Yogarajah ◽  
Phuong L. Nguyen ◽  
Rong He ◽  
Hassan B. Alkhateeb ◽  
Mithun Vinod Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Small Sample Size ◽  
Scoring Systems ◽  
Standard Of Care ◽  
Risk Groups ◽  
Small Sample ◽  
International Prognostic Scoring System ◽  
P Value ◽  
Number Of Patients

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

Multiple Copies of MLL Is The Most Commonly Detected Cytogenetic Abnormality In Newly Diagnosed Multiple Myeloma and May Modify Disease Risk

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1910-1910 ◽  
Author(s):  
Chrystal Landry ◽  
Dory Londono ◽  
Sean M. Devlin ◽  
Alex Lesokhin ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Protein Translation ◽  
Response To Therapy ◽  
Cytogenetic Abnormality ◽  
Newly Diagnosed

Abstract Background Multiple myeloma (MM) is a heterogeneous condition with variable disease course, response to therapy, and survival outcome. Cytogenetics and fluorescent in-situ hybridization (FISH) have identified several recurrent chromosomal aberrations in MM and play important and independent roles in risk stratification (Munshi et al. Blood 2011). However, the pathogenesis of the disorder remains poorly understood. Next-generation sequencing has recently identified that MM involves mutations of genes with roles in protein translation, histone methylation, and blood coagulation (Chapman et al. Nature 2011). Based on the observation that extra copies of MLL, a histone methyltransferase known to regulate the homeotic transcription factor HOXA9 that is highly expressed in MM, is frequently detected in MM, we sought to define the incidence and prognostic significance of excess MLL in MM patients. Methods We identified 188 patients with newly diagnosed MM who had cytogenetics and/or FISH performed on initial, pre-treatment bone marrow specimens at Memorial Sloan-Kettering Cancer Center between January 2009 and December 2012. Standard karyotype and FISH were performed as previously described (Cigudosa et al. Blood 1998, Gerritsen et al. Blood 1992). Probes included LSI IgH/FGF3, LSI IgH/CCND1, LSI IgH/MAF, LSI MLL, LSI p53/cep17, LSI13q14.3/13q34, LSI ETV6, LSI CBFB, LSI 1p36/1q25, and LSI 5,9,15 from Abbott Molecular. Fisher's exact test evaluated the association between MLL and selected abnormalities. Kaplan-Meier methodology estimated overall survival from the date of BM evaluation, and survival was compared using a logrank test. Results In unselected bone marrow specimens, abnormalities were detected by karyotype in 17% (27/156) and FISH in 47% (87/186) of patients tested. Hyperdiploidy, which has been associated with longer survival, was identified in 23% (43/187) of patients, while the unfavorable risk abnormalities, including loss of p53, deletion 13q (by karyotype), translocation (4;14) and excess 1q were seen in 8% (15/179), 8% (12/156), 4% (7/176) and 16% (29/178) of patients, respectively. Translocation (11;14) was seen in 4 patients; translocation (14;16) was not identified in any patient. 28% (51/183) of patients had extra copies of MLL, which was the most frequent genetic abnormality identified. Unexpectedly, this abnormality was significantly associated with both favorable (hyperdiploidy, P = <0.001) and unfavorable (deletion 13q, P = 0.043; excess 1q P = 0.001) risk genetics. While having excess MLL had no impact on the overall survival of standard-risk patients, defined as neither hyperdiploid nor with unfavorable genetics (N = 100), patients with poor-risk genetics (N = 46) and extra copies of MLL had a trend toward better survival, P = 0.06 (Figure 1). Conclusions Karyotype and FISH studies identified excess MLL as the most frequent cytogenetic abnormality in a large cohort of newly diagnosed MM patients. In patients with MM and unfavorable cytogenetics, the presence of excess MLL may ameliorate some of the adverse impact of associated with these abnormalities. Understanding the functional significance of excess MLL, perhaps as it relates to frequently dysregulated HOXA9 in MM, may provide insight into disease pathogenesis and/or identify drugable targets. Disclosures: No relevant conflicts of interest to declare.

Longitudinal whole body MRI (wbMRI) in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8590-8590
Author(s):  
Maximilian Merz ◽  
Barbara Wagner-Gund ◽  
Kai Neben ◽  
Anthony D. Ho ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Whole Body ◽  
Rank Test ◽  
Focal Lesions ◽  
Patients At Risk ◽  
Initial Work

8590 Background: The detection of bone marrow focal lesions (FLs) by MRI at the initial work up has prognostic significance in multiple myeloma (MM), smoldering MM as well as MGUS. Currently, there are no data available on the predictive relevance of new FLs or FLs increasing in size in longitudinally performed wbMRIs for the follow-up of sMM and MGUS. Methods: We retrospectively analyzed 87 patients (sMM n=65; MGUS n=22) that received at least 2 (up to 5) wbMRIs for follow-up. The date of progression into MM requiring systemic therapy was defined as event for the analysis of progression free survival (PFS). Radiological progressive disease (rPD) was defined as the appearance of novel FLs or increase in size of preexisting FLs. Kaplan-Meier plots of PFS for patients with rPD and patients without rPD were analyzed using the log-rank test for significant differences. Results: Median follow-up was 61 months (9.8-101) with a median time between follow-up wbMRIs of 15.8 months (1-73). Progression from sMM/MGUS into MM was found in 28 patients (sMM 40%; MGUS 9%). Using wbMRI, rPD was found in 21 patients (sMM 32%; MGUS 0%). Of all patients, 76% (n=16) with rPD and 16% (n= 9) without rPD progressed into MM during the observation period. Analysis of Kaplan Meyer plots for PFS revealed a highly significant shorter PFS for patients with rPD (32 months) compared to patients with radiological stable disease in wbMRI (PFS not reached; p<0.0001). New appearance or progression of diffuse bone marrow infiltration was not associated with a shorter PFS (not reached; p>0.05). Conclusions: In our study, the appearance of novel FLs or progression of preexisting FLs was highly predictive for progression from sMM into MM requiring systemic treatment. We conclude that wbMRI is effective for the longitudinal follow-up of patients with sMM and MGUS and identifies a group of patients at risk for progression into MM.

MAGE-A3 or NY-ESO1 Expression and Spontaneous Antibody Responses to NY-ESO1 in Newly Diagnosed Multiple Myeloma Patients Are Associated with Worse Overall Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5110-5110
Author(s):  
Adam D Cohen ◽  
Ping Lu ◽  
Sacha Gnjatic ◽  
James Hoffman ◽  
Erika Ritter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Soft Tissue ◽  
Induction Therapy ◽  
Plasma Cells ◽  
Prognostic Significance ◽  
Antibody Responses ◽  
Newly Diagnosed ◽  
Bone Marrow Plasma

Abstract The cancer-testis antigens (CTA) are highly immunogenic antigens expressed in various tumors but not in normal tissues (except during gametogenesis), making them an attractive target for cancer immunotherapy. Expression of CTAs such as MAGE-A3, MAGE-C1 (CT7), MAGE-C2 (CT10), NY-ESO1 and the SSX antigens has been previously reported in multiple myeloma (MM). To date, however, these reports have included a heterogeneous group of newly diagnosed and relapsed/refractory patients, all in different stages of treatment. Therefore, the extent and prognostic significance of CTA expression, and of de novo immune responses against CTA in newly-diagnosed MM patients are not known. We now report on both CTA expression and antibody responses in MM patients at diagnosis and on their prognostic significance. From 8/00-11/04, we treated 67 newly-diagnosed, symptomatic patients with a thalidomide, doxorubicin, and dexamethasone-based induction regimen. (Brit J Haematol2006;132:155). Median age was 58; 54% were ISS stage I, 28% ISS II, and 18% ISS III. Nine of 63 tested (14%) had deletion 13q by FISH, while 24% had soft tissue involvement by MM. Responses to induction therapy included 10 (15%) CR, 16 (24%) VGPR, 26 (39%) PR, 6 (8%) stable or progressive disease, and 9 (13%) inevaluable. Post-induction 54 underwent autoSCT and 9 also underwent alloSCT.. Median overall survival (OS) has not been reached with 61% alive at median follow up of 65 months. Cryopreserved pre-treatment bone marrow plasma cells were used to assess CTA expression by RT-PCR. Pre- and post-treatment sera were used to assess antibody (Ab) responses against CTA proteins by ELISA. Fifty-two patients had sufficient RNA for PCR, and 46 had baseline serum for ELISA. OS of these groups did not differ significantly from the entire cohort. At least 1 CTA was expressed in 77% of cases, including MAGE-A3 (52%), SSX1 (40%), CT7 (29%), CT10 (25%), NY-ESO1 (21%), and SSX5 (17%). Three or more CTA were expressed in 29% of cases. Individually MAGE-A3 or NY-ESO1 expression at diagnosis conferred a poorer prognosis (MAGE-A3: median OS 66 mos. vs. not reached, p=0.02 by log-rank; NY-ESO1: median OS 65 mos. vs. not reached, p=0.09). These poorer outcomes were independent of ISS stage, presence of del 13q, or response to induction therapy. No other CTA was associated with an OS difference, nor was the total number of CTA expressed prognostically significant. Baseline Ab responses, all at titers &gt; 1:1600, were noted to NY-ESO1 in 6/46 (13%) patients, 5 of whom also had Ab to the NY-ESO1 homologue LAGE-1. Ab responses were also noted to CT7 (n=2), CT10 (n=1) and SSX4 (n=1). No Ab responses were noted to MAGE-A3. The effect of induction therapy on antibody titers was inconsistent, with increases, decreases, and no changes seen. Interestingly, 2 of the 6 NY-ESO1 Ab+ patients had no NY-ESO1 expression in bone marrow plasma cells. Both, however, had extensive soft tissue (ST) plasmacytomas, suggesting another source of NY-ESO1 antigen. Presence of NY-ESO1 Ab correlated significantly with baseline ST involvement, with 67% of Ab+ patients having ST disease compared with 20% of Ab− patients (p=0.05). NY-ESO1 Ab+ patients also had significantly poorer OS (med 21 mos. vs. not reached, p=0.009), independent of other prognostic factors. In sum, CTA expression is frequent in newly diagnosed MM patients, and expression of MAGE-A3 or NY-ESO1 is associated with worse long-term survival. Spontaneous antibody responses against NY-ESO1 are seen in untreated patients, and are associated with ST involvement and poorer survival. Further exploration of biologic differences between CTA+ and CTA-MM, as well as immunotherapeutic strategies which target these antigens, are warranted.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Outcomes of Surgical and Nonsurgical Treatment for Colorectal Cancer in Nonagenarian Patients

2021 ◽  
pp. 000313482199506
Author(s):  
Youngbae Jeon ◽  
Kyoung-Won Han ◽  
Won-Suk Lee ◽  
Jeong-Heum Baek
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Postoperative Mortality ◽  
Nonsurgical Treatment ◽  
Perioperative Outcomes ◽  
Rank Test ◽  
Kaplan Meier ◽  
Number Of Patients

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.

Risk of Metastatic Ovarian Involvement in Nongynecologic Malignancies

2012 ◽  
Vol 22 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Kidong Kim ◽  
Soo Youn Cho ◽  
Sang-Il Park ◽  
Hye Jin Kang ◽  
Beob-Jong Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Tumors ◽  
Rank Test ◽  
Benign Tumors ◽  
Binary Logistic Regression Analysis ◽  
Fisher Exact Test ◽  
Tumor Type ◽  
Metastatic Tumors ◽  
Number Of Patients ◽  
Adnexal Tumors

ObjectiveThe objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors.MethodsThe eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test.ResultsIn 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers.ConclusionOne hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

scholarly journals Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma

2005 ◽  
Vol 16 (11) ◽  
pp. 1824-1828 ◽  
Author(s):  
L.A. Moulopoulos ◽  
D. Gika ◽  
A. Anagnostopoulos ◽  
K. Delasalle ◽  
D. Weber ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
Prognostic Significance ◽  
Resonance Imaging

scholarly journals Increased expression of cyclin-D1 on trephine bone marrow biopsies independently predicts for shorter overall survival in patients with multiple myeloma treated with novel agents

2012 ◽  
Vol 87 (7) ◽  
pp. 734-736 ◽  
Author(s):  
Anna Tasidou ◽  
Maria Roussou ◽  
Evangelos Terpos ◽  
Efstathios Kastritis ◽  
Maria Gkotzamanidou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Novel Agents ◽  
Bone Marrow Biopsies

scholarly journals Prognostic significance of esterase gene expression in multiple myeloma

2021 ◽  
Author(s):  
Romika Kumari ◽  
Muntasir Mamun Majumder ◽  
Juha Lievonen ◽  
Raija Silvennoinen ◽  
Pekka Anttila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Genomic Variation ◽  
High Expression ◽  
Genetic Profile ◽  
Esterase Gene ◽  
Low Expression

Abstract Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

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