Serological identification and bioinformatics analysis of immunogenic antigens in multiple myeloma

Zhou, Fuling; Zhang, W. G.; Chen, G.; Zhao, Wanhong; Cao, Xing‐Mei; Chen, Y. X.; Liu, J.; Liu, S. H.

doi:10.1007/s00262-005-0074-x

Cited by 12 publications

(11 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The existing MMSA-8 sequences were used as a guide to design primers using Primer Premier 5.0 (12). Briefly, total RNA was isolated using TRIzol (Gibco-BRL, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

“…We serologically assessed tumor antigens using a recombinant cDNA expression library (SEREX) of MM to identify MM-associated antigens (MMSAs). MMSA-8 was confirmed as a new antigen that specifically interacted with the serum from patients with allogeneic myeloma but did not interact with normal donors (12). Differences in the MMSA-8 sequence with the novel available working version of the human genome suggests that MMSA-8 is a new RPS27A-related transcription variant that is specifically associated with MM.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification and expression of MMSA-8, and its clinical significance in multiple myeloma

Yang

Zhang

et al. 2017

Oncology Reports

View full text Add to dashboard Cite

In our previous studies, we identified 12 multiple myeloma (MM)-associated antigens by serological analysis of tumor-associated antigens with a recombinant cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one of the new antigens identified. We determined the 3′- and 5′-ends of MMSA-8 using SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A-related transcript variant 1 that is specifically associated with MM. We examined its prognostic significance for the first time, by investigating the correlations between MMSA-8 expression and definite clinicopathological features. We quantitatively assessed MMSA-8 expression using qRT-PCR and western blot analysis in healthy donors and MM patients. The expression levels of MMSA-8 were upregulated with statistical significance in MM patients in contrast to those in healthy donors. The expression of MMSA-8 was also upregulated in relapsed patients compared with that in the complete remission (CR) group. Contrasting MMSA-8 expression levels in different patients with definite clinicopathological features suggested an association between MMSA-8 with unfavorable clinicopathological characteristics, such as international staging system (ISS) stage III, higher lactate dehydrogenase (LDH) levels and higher C-reactive protein (CRP) levels. The expression of MMSA-8 was also increased in patients with unfavorable cytogenetic and genetic abnormalities, including the presence of t(11;14), t(4;14), t(14;16), del(17p), del(13q) and p53 deletion, which was statistically significant. The expression of MMSA-8 exhibited significant variance in the treatment responses of the CR, PR, progression and relapse groups. Univariate and multivariate analyses revealed that high MMSA-8 values were associated with poorer progression-free survival (PFS) and overall survival (OS) in MM patients independently. In conclusion, our data indicated that MMSA-8 is an independent and unfavorable prognostic risk factor in MM; MMSA-8 is also a promising diagnostic and therapeutic target in MM patients, but further validation is needed.

show abstract

“…The existing MMSA-8 sequences were used as a guide to design primers using Primer Premier 5.0 (12). Briefly, total RNA was isolated using TRIzol (Gibco-BRL, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification and expression of MMSA-8, and its clinical significance in multiple myeloma

Yang

Zhang

et al. 2017

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…Apart from the results of a few SEREX (serological identification of antigens by recombinant expression cloning)-based studies, 41,42 B-cell antitumor immunity is insufficiently understood in myeloma compared with the considerable amount of data on T-cell-mediated immunity in this disease. 25,[43][44][45][46] Here, we profiled epitope recognition in a cohort of 18 patients after allogeneic or autologous HSCT or novel agent therapy, revealing strikingly disease-specific and overlapping patterns of epitope reactivity.…”

Section: Discussionmentioning

confidence: 99%

A transplant “immunome” screening platform defines a targetable epitope fingerprint of multiple myeloma

Schieferdecker

Oberle

Thiele

et al. 2016

Blood

View full text Add to dashboard Cite

Key Points• The myeloma transplant B-cell immunome is predictive for response to treatment.• It may be exploited by immunosequencing and library technology as a source for unique target structures and antibodies for immunotherapy.Multiple myeloma (MM) is a hematological cancer for which immune-based treatments are currently in development. Many of these rely on the identification of highly diseasespecific, strongly and stably expressed antigens. Here, we profiled the myeloma B-cell immunome both to explore its predictive role in the context of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and to identify novel immunotherapeutic targets. We used random peptide phage display, reverse immunization, and nextgeneration sequencing-assisted antibody phage display to establish a highly myelomaspecific epitope fingerprint targeted by B-cell responses of 18 patients in clinical remission. We found that allogeneic HSCT more efficiently allowed production of myeloma-specific antibodies compared with autologous HSCT and that a highly reactive epitope recognition signature correlated with superior response to treatment. Next, we performed myeloma cell surface screenings of phage-displayed patient transplant immunomes. Although some of the screenings yielded clear-cut surface binders, the majority of screenings did not, suggesting that many of the targeted antigens may in fact not be accessible to the B-cell immune system in untreated myeloma cells. This fit well with the identification of heat-shock proteins as a class of antigens that showed overall the broadest reactivity with myeloma patient sera after allogeneic HSCT and that may be significantly translocated to the cell surface upon treatment as a result of immunogenic cell death. Our data reveal a disease-specific epitope signature of MM that is predictive for response to treatment. Mining of transplant immunomes for strong myeloma surface binders may open up avenues for myeloma immunotherapy. (Blood. 2016;127(25):3202-3214)

show abstract

“…7, KLF10 also appears to play a role in other cancers, including human prostate cancer (as EGRα) [52,60,61], pancreatic cancers [26,53,59,62], human colo-rectal cancer [63], lymphoma cells [37,64], non-small cell carcinoma [65], renal cell carcinoma [66], multiple myeloma [67], and finally, brain cancers [57]. The above studies strongly support that KLF10 plays an important role in inhibiting cell proliferation and inducing apoptosis.…”

Section: Phenotypic and Disease Implications Of Klf10mentioning

confidence: 99%

Functional role of KLF10 in multiple disease processes

et al. 2010

View full text Add to dashboard Cite

Since the discovery by this laboratory of the zinc finger transcription factor, KLF10, a member of the Krüppel-like family of transcription factors, there have been multiple publications regarding its functions and its immediate family members, in numerous cell types. KLF10 has been shown to be rapidly induced by TGFβ1, 2, 3, E2, epidermal growth factor, and bone morphogenetic protein-2. TGFβ inducible early gene-1 activates the TGFβ-Smad signaling pathway via repression of Smad 7 expression and activation of Smad 2 expression and activity. Overall, KLF10 has been implicated in cell differentiation, as a target gene for a variety of signaling pathways, and in serving as a potential marker for human diseases such as breast cancer, cardiac hypertrophy, and osteoporosis. Like other KLF members, KLF10 is expressed in specific cell types in numerous tissues and is known to be involved in repressing cell proliferation and inflammation as well as inducing apoptosis similar to that of TGFβ KLF10 binds to Sp-1-GC rich DNA sequences and can activate or repress the transcription of a number of genes. Overall, KLF10 has been shown to play a major role in the TGFβ inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGFβ.

show abstract

Serological identification and bioinformatics analysis of immunogenic antigens in multiple myeloma

Cited by 12 publications

References 41 publications

Identification and expression of MMSA-8, and its clinical significance in multiple myeloma

Identification and expression of MMSA-8, and its clinical significance in multiple myeloma

A transplant “immunome” screening platform defines a targetable epitope fingerprint of multiple myeloma

Functional role of KLF10 in multiple disease processes

Contact Info

Product

Resources

About