Prognostic Significance of Chromosome 13q14 Deletion and Expression of Cd19, Cd28 and Cd117 in Multiple Myeloma

2015 ◽  
Vol 66 (4-6) ◽  
pp. 371-384
Author(s):  
Manal Hashem Fayek ◽  
Manal Mohamed Ismail ◽  
Dina Aziz Khattab ◽  
Tamer Mohamed Ahmed ◽  
Deena Samir Mohamed ◽  
...  

Oncotarget ◽  
2015 ◽  
Vol 6 (35) ◽  
pp. 38270-38282 ◽  
Author(s):  
Fei Li ◽  
Yan Xu ◽  
Shuhui Deng ◽  
Zengjun Li ◽  
Dehui Zou ◽  
...  


2018 ◽  
Author(s):  
Weilong Zhang ◽  
Rui Lai ◽  
Xue He ◽  
Xiaoni Liu ◽  
Ye Zhang ◽  
...  


Cancer ◽  
2021 ◽  
Author(s):  
Sophia Scheubeck ◽  
Gabriele Ihorst ◽  
Katja Schoeller ◽  
Maximilian Holler ◽  
Mandy‐Deborah Möller ◽  
...  


2009 ◽  
Vol 144 (2) ◽  
pp. 266-268 ◽  
Author(s):  
T. Sutlu ◽  
E. Alici ◽  
M. Jansson ◽  
A. Wallblom ◽  
M. S. Dilber ◽  
...  


2005 ◽  
Vol 16 (11) ◽  
pp. 1824-1828 ◽  
Author(s):  
L.A. Moulopoulos ◽  
D. Gika ◽  
A. Anagnostopoulos ◽  
K. Delasalle ◽  
D. Weber ◽  
...  


Author(s):  
Romika Kumari ◽  
Muntasir Mamun Majumder ◽  
Juha Lievonen ◽  
Raija Silvennoinen ◽  
Pekka Anttila ◽  
...  

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.



Author(s):  
Hadiyah Y. Audil ◽  
Joselle M. Cook ◽  
Patricia T. Greipp ◽  
Prashant Kapoor ◽  
Linda B. Baughn ◽  
...  


2019 ◽  
Vol Volume 11 ◽  
pp. 9409-9420
Author(s):  
Siwei Liu ◽  
Jie Shi ◽  
Honggang Guo ◽  
Fangfang Xu ◽  
Min Wei ◽  
...  


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Chenxing Du ◽  
Xue-Han Mao ◽  
Jiahui Liu ◽  
Huishou Fan ◽  
Weiwei Sui ◽  
...  

Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.



Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Frits van Rhee ◽  
Vanessa Bolejack ◽  
Klaus Hollmig ◽  
Mauricio Pineda-Roman ◽  
Elias Anaissie ◽  
...  

Abstract Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain–only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain–only secretion (P < .001), creatinine level 176.8 μM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline—reflecting more aggressive disease—and steeper reductions after therapy identified patients with inferior survival.



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