Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia

Skou, Anne-Sofie; Juul-Dam, Kristian Løvvik; Hansen, Maria; Stratmann, Svea; Holmfeldt, Linda; Aggerholm, Anni; Nyvold, Charlotte Guldborg; Ommen, Hans Beier; Hasle, Henrik

doi:10.1016/j.jmoldx.2021.09.004

Cited by 3 publications

(3 citation statements)

References 40 publications

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“…26 Skou and colleagues reported that SPAG6 overexpression in PB may predict relapse in childhood AML patients. 27 In line with these studies in hematological neoplasms, we found that SPAG6 was significantly upregulated in adult AML, which was negatively correlated with the overall survival rate of AML patients. In addition, functional assays of leukemia cells show a tumor-promoting function for SPAG6 in AML.…”

Section: Discussionsupporting

confidence: 85%

Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression

Yuan

Luo

et al. 2022

Blood Advances

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Chromosomal aberrations and gene mutations have been considered to be the major reasons for high recurrence rates and poor survival among AML patients. However, the underlying molecular mechanism of AML gene mutation remains largely unclear. Here, we show that sperm-associated antigen 6 (SPAG6), one of the most markedly increased SPAG genes in AML, significantly contributed to the proliferation and migration of leukemic cells. SPAG6 was highly expressed in AML and its upregulation was negatively correlated with the prognosis of the disease. In vitro, SPAG6 promoted the proliferation and migration of leukemia cells and promoted cell cycle progression from G1 phase to S phase. In vivo, low expression of SPAG6 reduced the proliferation and infiltration of leukemia cells and prolonged the survival of xenograft tumor mice. Furthermore, immunoprecipitation and mass spectrometry analysis showed that SPAG6 interacts with MYO1D. Specifically, overexpression of SPAG6 promoted the translocation of MYO1D into the cell membrane, thus upgrading the expression level of the EGFR family and thereby promoting the progression of AML. Overall, our study found that SPAG6 combined with MYO1D and translocated MYO1D from the cytosol to the cytomembrane, which induced the PI3K/AKT signaling and ERK signaling pathway to regulate the growth and prognosis of AML. SPAG6 may become a new target gene for the treatment of AML.

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Section: Discussionsupporting

confidence: 85%

Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression

Yuan

Luo

et al. 2022

Blood Advances

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“…PRAME is not present or is expressed at extremely low levels in the majority of normal tissues, such as the testis, ovary, adrenal, endometrium, placenta, bone marrow, CD34 + hematopoietic progenitors, unsorted peripheral blood cells, and sorted B and T lymphocytes ( 6 , 31 , 34 – 38 ). However, it is highly expressed in numerous types of human malignancies, including most primary and metastatic melanomas ( 6 ), ovarian cancer ( 16 ), breast carcinoma ( 39 ), lung carcinomas ( 40 ), neuroblastoma ( 41 ), cervical cancer ( 25 ), and head and neck cancers ( 42 ).…”

Section: Expression Of Prame In Normal Hematopoietic and Aml Cellsmentioning

confidence: 99%

“…The results indicate that PRAME serves as a reliable indicator for identifying MRD status and detecting relapse prior to both morphologic and molecular relapse, particularly in individuals lacking identifiable genetic markers ( 49 , 80 , 81 ). In addition, some studies have shown that PRAME, along with other LAAs, can serve as a tool for monitoring MRD and predicting recurrence ( 38 , 82 ). In addition to providing AML patients with either a positive or a more sensitive molecular marker for MRD monitoring, simultaneous detection of PRAME and other LAAs could also prevent false negatives ( 54 ).…”

Section: Minimal Residual Disease Monitoringmentioning

confidence: 99%

Targeting PRAME for acute myeloid leukemia therapy

Yang,

Chen,

et al. 2024

Front. Immunol.

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Despite significant progress in targeted therapy for acute myeloid leukemia (AML), clinical outcomes are disappointing for elderly patients, patients with less fit disease characteristics, and patients with adverse disease risk characteristics. Over the past 10 years, adaptive T-cell immunotherapy has been recognized as a strategy for treating various malignant tumors. However, it has faced significant challenges in AML, primarily because myeloid blasts do not contain unique surface antigens. The preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, is abnormally expressed in AML and does not exist in normal hematopoietic cells. Accumulating evidence has demonstrated that PRAME is a useful target for treating AML. This paper reviews the structure and function of PRAME, its effects on normal cells and AML blasts, its implications in prognosis and follow-up, and its use in antigen-specific immunotherapy for AML.

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SPAG6 regulates cell proliferation and apoptosis via TGF-β/Smad signal pathway in adult B-cell acute lymphoblastic leukemia

Zhao,

Yin,

Ding

et al. 2023

Int J Hematol

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Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia

Cited by 3 publications

References 40 publications

Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression

Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression

Targeting PRAME for acute myeloid leukemia therapy

SPAG6 regulates cell proliferation and apoptosis via TGF-β/Smad signal pathway in adult B-cell acute lymphoblastic leukemia

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