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

Anne Sofie Skou; Kristian L. Juul-Dam; Maria Hansen; Birgitte Lausen; Svea Stratmann; Linda Holmfeldt; Anni Aggerholm; Charlotte G. Nyvold; Hans B. Ommen; Henrik Hasle

doi:10.1016/j.jmoldx.2021.09.004

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

Anne Sofie Skou^*, Kristian L. Juul-Dam, Maria Hansen, Birgitte Lausen, Svea Stratmann, Linda Holmfeldt, Anni Aggerholm, Charlotte G. Nyvold, Hans B. Ommen, Henrik Hasle

^*Corresponding author for this work

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Abstract

Overexpressed genes may be useful for monitoring of measurable residual disease (MRD) in patients with childhood acute myeloid leukemia (AML) without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n = 53) and children with suspected infection (n = 90). Gene expression at AML diagnosis (n=50) and during follow-up (n = 21) was compared with child-specific reference values. At diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median, five samples/patient; range, 1 to 10) during follow-up in 21 patients with high expression at diagnosis. All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of 2 months (range, 0.6 to 9.6 months) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1 of 130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate MRD monitoring in most patients without a leukemia-specific target.

Original language	English
Journal	Journal of Molecular Diagnostics
Volume	23
Issue	12
Pages (from-to)	1787-1799
Number of pages	13
ISSN	1525-1578
DOIs	https://doi.org/10.1016/j.jmoldx.2021.09.004
Publication status	Published - Dec 2021

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Skou, A. S., Juul-Dam, K. L., Hansen, M., Lausen, B., Stratmann, S., Holmfeldt, L., Aggerholm, A., Nyvold, C. G., Ommen, H. B., & Hasle, H. (2021). Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia. Journal of Molecular Diagnostics, 23(12), 1787-1799. https://doi.org/10.1016/j.jmoldx.2021.09.004

@article{41adf15ca34d4afe9c0cfcca348a311d,

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

abstract = "Overexpressed genes may be useful for monitoring of measurable residual disease (MRD) in patients with childhood acute myeloid leukemia (AML) without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n = 53) and children with suspected infection (n = 90). Gene expression at AML diagnosis (n=50) and during follow-up (n = 21) was compared with child-specific reference values. At diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median, five samples/patient; range, 1 to 10) during follow-up in 21 patients with high expression at diagnosis. All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of 2 months (range, 0.6 to 9.6 months) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1 of 130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate MRD monitoring in most patients without a leukemia-specific target.",

author = "Skou, {Anne Sofie} and Juul-Dam, {Kristian L.} and Maria Hansen and Birgitte Lausen and Svea Stratmann and Linda Holmfeldt and Anni Aggerholm and Nyvold, {Charlotte G.} and Ommen, {Hans B.} and Henrik Hasle",

note = "Publisher Copyright: {\textcopyright} 2021 Association for Molecular Pathology and American Society for Investigative Pathology",

year = "2021",

month = dec,

doi = "10.1016/j.jmoldx.2021.09.004",

language = "English",

volume = "23",

pages = "1787--1799",

journal = "Journal of Molecular Diagnostics",

issn = "1525-1578",

publisher = "Elsevier B.V.",

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}

Skou, AS, Juul-Dam, KL, Hansen, M, Lausen, B, Stratmann, S, Holmfeldt, L, Aggerholm, A, Nyvold, CG, Ommen, HB & Hasle, H 2021, 'Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia', Journal of Molecular Diagnostics, vol. 23, no. 12, pp. 1787-1799. https://doi.org/10.1016/j.jmoldx.2021.09.004

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 L.; Hansen, Maria et al.
In: Journal of Molecular Diagnostics, Vol. 23, No. 12, 12.2021, p. 1787-1799.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia

AU - Skou, Anne Sofie

AU - Juul-Dam, Kristian L.

AU - Hansen, Maria

AU - Lausen, Birgitte

AU - Stratmann, Svea

AU - Holmfeldt, Linda

AU - Aggerholm, Anni

AU - Nyvold, Charlotte G.

AU - Ommen, Hans B.

AU - Hasle, Henrik

PY - 2021/12

Y1 - 2021/12

N2 - Overexpressed genes may be useful for monitoring of measurable residual disease (MRD) in patients with childhood acute myeloid leukemia (AML) without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n = 53) and children with suspected infection (n = 90). Gene expression at AML diagnosis (n=50) and during follow-up (n = 21) was compared with child-specific reference values. At diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median, five samples/patient; range, 1 to 10) during follow-up in 21 patients with high expression at diagnosis. All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of 2 months (range, 0.6 to 9.6 months) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1 of 130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate MRD monitoring in most patients without a leukemia-specific target.

AB - Overexpressed genes may be useful for monitoring of measurable residual disease (MRD) in patients with childhood acute myeloid leukemia (AML) without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n = 53) and children with suspected infection (n = 90). Gene expression at AML diagnosis (n=50) and during follow-up (n = 21) was compared with child-specific reference values. At diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median, five samples/patient; range, 1 to 10) during follow-up in 21 patients with high expression at diagnosis. All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of 2 months (range, 0.6 to 9.6 months) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1 of 130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate MRD monitoring in most patients without a leukemia-specific target.

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U2 - 10.1016/j.jmoldx.2021.09.004

DO - 10.1016/j.jmoldx.2021.09.004

M3 - Journal article

C2 - 34600138

AN - SCOPUS:85117924972

SN - 1525-1578

VL - 23

SP - 1787

EP - 1799

JO - Journal of Molecular Diagnostics

JF - Journal of Molecular Diagnostics

IS - 12

ER -

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

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