Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia.

Narayanan, Nisha; Marvin-Peek, Jennifer; Abouelnaaj, Mohamad K; Majid, Dhabya; Wang, Bofei; Brown, Brandon D; Qiu, Yihua; Kornblau, Steven M; Abbas, Hussein A

Narayanan, Nisha; Marvin-Peek, Jennifer; Abouelnaaj, Mohamad K; Majid, Dhabya; Wang, Bofei; Brown, Brandon D; Qiu, Yihua; Kornblau, Steven M; Abbas, Hussein A.

Afiliación

Narayanan N; Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Marvin-Peek J; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Abouelnaaj MK; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Majid D; Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Wang B; University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas 77030, United States.
Brown BD; Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Qiu Y; Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Kornblau SM; Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Abbas HA; Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.

J Proteome Res ; 23(7): 2495-2504, 2024 Jul 05.

Article en En | MEDLINE | ID: mdl-38829961

ABSTRACT

ABSTRACT

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower than those of AML without deletion 7/7q, this observation was not significant. Low ASNS expression correlated with improved overall survival (46 versus 54 weeks, respectively, p = 0.011), whereas higher ASNS levels were associated with better response to venetoclax-based therapy. Protein correlation analysis demonstrated association between ASNS and proteins involved in methylation and DNA repair. In conclusion, while ASNS expression was not lower in patients with deletion 7/7q as initially predicted, ASNS levels were highly variable across AML patients. Further studies are needed to assess whether patients with low ASNS expression are susceptible to asparaginase-based therapy due to their inability to augment compensatory ASNS expression upon asparagine depletion.

Asunto(s)

Aspartatoamoníaco Ligasa; Leucemia Mieloide Aguda; Proteómica; Humanos; Leucemia Mieloide Aguda/genética; Leucemia Mieloide Aguda/metabolismo; Leucemia Mieloide Aguda/tratamiento farmacológico; Aspartatoamoníaco Ligasa/genética; Aspartatoamoníaco Ligasa/metabolismo; Femenino; Proteómica/métodos; Masculino; Persona de Mediana Edad; Adulto; Anciano; Deleción Cromosómica; Análisis por Matrices de Proteínas/métodos; Asparaginasa/uso terapéutico; Asparaginasa/genética; Cromosomas Humanos Par 7/genética; Adulto Joven; Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N

Palabras clave

acute myeloid leukemia (AML); asparagine synthetase (ASNS); chromosome 7/7q deletion; reverse phase proteomics array (RPPA); venetoclax

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aspartatoamoníaco Ligasa / Leucemia Mieloide Aguda / Proteómica Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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