Prognostic significance of MYC oncoprotein expression on survival outcome in patients with acute myeloid leukemia with myelodysplasia related changes (AML-MRC)

Seongseok Yun, R. Sharma, O. Chan, Nicole D. Vincelette, David A. Sallman, Kendra Sweet, Eric Padron, Rami Komrokji, Jeffrey E. Lancet, Ivo L Abraham, Lynn C. Moscinski, John L. Cleveland, Alan F. List, Ling Zhang

Research output: Contribution to journalArticle

Abstract

MYC is an oncoprotein that coordinates the expression of genes involved in metabolism, cell differentiation and survival in various types of malignancies. However, the underlying oncogenic mechanisms and the clinical significance of MYC expression in the acute myeloid leukemia with myelodysplasia related changes (AML-MRC) remain to be answered. A total of 135 patients were retrospectively identified using Total Cancer Care (TCC) Moffitt Cancer Center (MCC) databases. Diagnosis of AML-MRC was based on the 2016 WHO classification utilizing bone marrow (BM) evaluation. MYC protein expression level was assessed by immunohistochemistry (IHC) staining using paraffin-embedded BM trephine biopsy samples obtained at the time of diagnosis or relapse. Concurrent somatic mutations were assessed using targeted next generation sequencing that include 54 genes. A total of 38% (n = 51) and 62% (n = 84) patients had high and low MYC expression, respectively. The most common somatic mutation in our cohort was TP53 followed by DNMT3A, and ASXL1. The median OS was significantly longer in low MYC patients (median OS 42.3 vs. 17.05 months, p = 0.0109). Multivariate analysis including MYC expression level, transplantation status, gender and age demonstrated high MYC expression (HR 1.77, 95% CI 1.004–3.104, p = 0.045) to be an independent poor prognostic factor. Further studies are needed to identify the underlying mechanism of MYC driven oncogenesis in AML-MRC. Additionally, the prognostic impact of MYC on the AML survival in a larger cohort that include diverse somatic mutations and chromosomal abnormalities requires further investigation.

Original languageEnglish (US)
Article number106194
JournalLeukemia Research
Volume84
DOIs
StatePublished - Sep 1 2019

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Oncogene Proteins
Acute Myeloid Leukemia
Mutation
Survival
Bone Marrow
Neoplasms
Chromosome Aberrations
Paraffin
Cell Differentiation
Cell Survival
Carcinogenesis
Multivariate Analysis
Transplantation
Immunohistochemistry
Databases
Staining and Labeling
Biopsy
Gene Expression
Recurrence
Genes

Keywords

  • MYC
  • sAML

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Prognostic significance of MYC oncoprotein expression on survival outcome in patients with acute myeloid leukemia with myelodysplasia related changes (AML-MRC). / Yun, Seongseok; Sharma, R.; Chan, O.; Vincelette, Nicole D.; Sallman, David A.; Sweet, Kendra; Padron, Eric; Komrokji, Rami; Lancet, Jeffrey E.; Abraham, Ivo L; Moscinski, Lynn C.; Cleveland, John L.; List, Alan F.; Zhang, Ling.

In: Leukemia Research, Vol. 84, 106194, 01.09.2019.

Research output: Contribution to journalArticle

Yun, S, Sharma, R, Chan, O, Vincelette, ND, Sallman, DA, Sweet, K, Padron, E, Komrokji, R, Lancet, JE, Abraham, IL, Moscinski, LC, Cleveland, JL, List, AF & Zhang, L 2019, 'Prognostic significance of MYC oncoprotein expression on survival outcome in patients with acute myeloid leukemia with myelodysplasia related changes (AML-MRC)', Leukemia Research, vol. 84, 106194. https://doi.org/10.1016/j.leukres.2019.106194
Yun, Seongseok ; Sharma, R. ; Chan, O. ; Vincelette, Nicole D. ; Sallman, David A. ; Sweet, Kendra ; Padron, Eric ; Komrokji, Rami ; Lancet, Jeffrey E. ; Abraham, Ivo L ; Moscinski, Lynn C. ; Cleveland, John L. ; List, Alan F. ; Zhang, Ling. / Prognostic significance of MYC oncoprotein expression on survival outcome in patients with acute myeloid leukemia with myelodysplasia related changes (AML-MRC). In: Leukemia Research. 2019 ; Vol. 84.
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abstract = "MYC is an oncoprotein that coordinates the expression of genes involved in metabolism, cell differentiation and survival in various types of malignancies. However, the underlying oncogenic mechanisms and the clinical significance of MYC expression in the acute myeloid leukemia with myelodysplasia related changes (AML-MRC) remain to be answered. A total of 135 patients were retrospectively identified using Total Cancer Care (TCC) Moffitt Cancer Center (MCC) databases. Diagnosis of AML-MRC was based on the 2016 WHO classification utilizing bone marrow (BM) evaluation. MYC protein expression level was assessed by immunohistochemistry (IHC) staining using paraffin-embedded BM trephine biopsy samples obtained at the time of diagnosis or relapse. Concurrent somatic mutations were assessed using targeted next generation sequencing that include 54 genes. A total of 38{\%} (n = 51) and 62{\%} (n = 84) patients had high and low MYC expression, respectively. The most common somatic mutation in our cohort was TP53 followed by DNMT3A, and ASXL1. The median OS was significantly longer in low MYC patients (median OS 42.3 vs. 17.05 months, p = 0.0109). Multivariate analysis including MYC expression level, transplantation status, gender and age demonstrated high MYC expression (HR 1.77, 95{\%} CI 1.004–3.104, p = 0.045) to be an independent poor prognostic factor. Further studies are needed to identify the underlying mechanism of MYC driven oncogenesis in AML-MRC. Additionally, the prognostic impact of MYC on the AML survival in a larger cohort that include diverse somatic mutations and chromosomal abnormalities requires further investigation.",
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AU - Yun, Seongseok

AU - Sharma, R.

AU - Chan, O.

AU - Vincelette, Nicole D.

AU - Sallman, David A.

AU - Sweet, Kendra

AU - Padron, Eric

AU - Komrokji, Rami

AU - Lancet, Jeffrey E.

AU - Abraham, Ivo L

AU - Moscinski, Lynn C.

AU - Cleveland, John L.

AU - List, Alan F.

AU - Zhang, Ling

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