Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease

Qin, Ya‐Zhen; Zhu, Hong‐Hu; Jiang, Bin; Li, Jinlan; Lu, Xi-jing; Li, Ling-di; Ruan, Guo‐Rui; Liu, YanRong; Chen, Shanshan; Huang, Xiao‐Jun

doi:10.1016/j.leukres.2008.08.026

Cited by 73 publications

(60 citation statements)

References 25 publications

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“…PRAME, which was first described in 1997 by Ikeda et al [36], has previously been shown to be expressed in 35-64% of AML patients [29,30,[37][38][39]. On the other hand, we have shown here that PRAME is absent from non-malignant hematopoetic cells, which is in line with our previous analysis of a panel of 23 healthy tissues including PBMC, BM samples, and CD341 progenitor cells from healthy donors [16].…”

Section: Discussionsupporting

confidence: 91%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N 5 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5 0 -aza-2 0 -deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2. Am. J. Hematol. 86:918-922, 2011. V

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Section: Discussionsupporting

confidence: 91%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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“…As a tumor-associated antigen (TAA), PRAME expression level is low in normal tissues and normal bone marrow, but it is highly increased in a variety of solid tumors and hematologic malignancies (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The majority of patients with acute myeloid leukemia (AML) overexpress PRAME (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, previous studies have reported that the majority of patients with myelodysplastic syndromes (MDS) overexpress PRAME (12,13). A high level of variation exists in the PRAME transcript levels for patients with AML and MDS (8)(9)(10)(11)(12)(13). In particular, the majority of patients with AML1-eight-twenty one (ETO) + AML and a number of patients with MDS overexpress PRAME with abnormally high increases (10,12,13).…”

Section: Introductionmentioning

confidence: 99%

“…A high level of variation exists in the PRAME transcript levels for patients with AML and MDS (8)(9)(10)(11)(12)(13). In particular, the majority of patients with AML1-eight-twenty one (ETO) + AML and a number of patients with MDS overexpress PRAME with abnormally high increases (10,12,13). PRAME transcript levels detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or quantitative PCR (qPCR) have been clinically used to determine the prognosis and monitor minimal residual disease (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Methylation pattern of preferentially expressed antigen of melanoma in acute myeloid leukemia and myelodysplastic syndromes

et al. 2017

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Abstract. Preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is overexpressed in a variety of hematologic malignancies with a great variation in expression. The majority of patients with acute myeloid leukemia (AML) 1-eight-twenty one (ETO) + AML and a certain number of myelodysplastic syndromes (MDS) have an abnormally high increase in PRAME expression level. The landscape of PRAME methylation requires evaluation in order to determine the most relevant sites and the exact association of its methylation with expression level and type of disease. In the present study, bone marrow samples collected from 8 AML1-ETO + AML, 4 MDS, 3 AML1-ETO -AML and 2 normal volunteers underwent bisulfate sequencing to analyze the methylation status of all four 5'-C-phosphate-G-3' (CpG) regions within the entire PRAME gene. The median PRAME transcript level of 15 patients was 204.5% (range, 0.02-710.3%). PRAME transcript levels were inversely associated with the degree of methylation of the -389 to -146 CpG sites (r=-0.69; P=0.002) in the 3' part of the promoter region and the +132 to +363 CpG sites (r=-0.69; P=0.006) in the exon 1b region. However, not every sample strictly followed this correlation: Certain samples with high degrees of methylation demonstrated abnormally high expression levels, and vice versa. The methylation ratios of CpG sites in exon 1a were low for all samples (range, 0.0-13.8%), and those in exon 2 were similar in 16 samples (range, 72.4-93.4%), with the exception of one patient with high expression (425.2%) and significantly low degree of methylation in the PRAME gene (22.2%). MDS patients revealed similar methylation ratios in the 3' section of the promoter region, but tended to have lower methylation ratios in the exon 1b region (P=0.62 and P=0.09, respectively) compared with those observed in AML1-ETO + patients with AML and similar degree of PRAME overexpression. Therefore, the hypomethylation of CpG sites in the 3' part of the promoter region and in exon 1b was typically found with PRAME overexpression in AML and MDS. Methylation of other CpG islands, epigenetic and genetic mechanisms, and type of disease may also be involved.

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“…PRAME mRNA was observed in about one-third of AML cases and there was a good correlation between PRAME mRNA level and hematological remission and relapse. It may be also useful marker to detect minimal residual disease after allogenic transplantation (Paydas et al, 2005;Qin et al ., 2009). Epping et al (2005) showed that PRAME is a repressor of retinoic acid signaling but did not confirm this mechanism in the pathogenesis of AML.…”

Section: Other Molecular Marker Genes Expressionmentioning

confidence: 99%

Molecular Markers for Risk Stratification in Adult Acute Myeloid Leukemia with Normal Cytogenetics

Fuchs¹

2011

Acute Leukemia - The Scientist's Perspective and Challenge

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Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease

Cited by 73 publications

References 25 publications

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

Methylation pattern of preferentially expressed antigen of melanoma in acute myeloid leukemia and myelodysplastic syndromes

Molecular Markers for Risk Stratification in Adult Acute Myeloid Leukemia with Normal Cytogenetics

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