Acute Myeloid Leukemia (AML): Upregulation of BAALC/MN1/MLLT11/EVI1 Gene Cluster Relate With Poor Overall Survival and a Possible Linkage With Coexpression of MYC/BCL2 Proteins.

Abstract

BACKGROUND:

Molecular heterogeneity accounts for the variable and often poor prognosis in acute myeloid leukemia (AML). The current risk stratification strategy in clinical practice is limited to karyotyping and limited molecular studies screening for genetic mutations such as FLT-3 and NPM1. There is opportunity to identify further molecular prognostic markers, which may also lay the groundwork for the development of novel targeted therapies. Complex molecular technologies require transition into widely available laboratory platforms, for better integration into routine clinical practice.

METHOD:

In a defined subset (MYC/BCL2 or MYC/BCL2) of AML patients (n=20), we examined expression signature of several genes (n=12) of established prognostic value in AML. RNA expression and MYC/BCL2 protein pattern was correlated with 3 cytogenetic risk groups and overall survival.

RESULTS:

K-means++ unsupervised clustering defined 2 distinct groups with high and low transcript levels of BAALC/MN1/MLLT11/EVI1/SOCS2 genes (>2.5-fold difference; P<0.001). This mRNA signature trended with higher prevalence of MYC/BCL2 coexpression (P<0.057) and poor overall survival (P<0.036), but did not correlate with conventional cytogenetic risk groups (P<0.084).

CONCLUSIONS:

This pilot study provides useful data, which may help further refine the prognostic scheme of AML patients outside conventional cytogenetic risk groups. It also presents some biological rationale for future studies to explore the use of novel agents targeting MYC and/or BCL2 genes in combination with conventional chemotherapy protocols for AML.

• Authors: Ariz Akhter, Fahad Farooq, Ghaleb Elyamany, Muhammad K Mughal, Fariborz Rashid-Kolvear, Meer-Taher Shabani-Rad, Lesley Street, Adnan Mansoor
• Journal: Applied immunohistochemistry & molecular morphology : AIMM (Appl Immunohistochem Mol Morphol) Vol. 26 Issue 7 Pg. 483-488 (08 2018) ISSN: 1533-4058 [Electronic] United States
• PMID: 28362701 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAALC protein, human
• BCL2 protein, human
• MDS1 and EVI1 Complex Locus Protein
• MECOM protein, human
• MLLT11 protein, human
• MN1 protein, human
• MYC protein, human
• NPM1 protein, human
• Neoplasm Proteins
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-myc
• Trans-Activators
• Tumor Suppressor Proteins
• Nucleophosmin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Disease-Free Survival
• Female
• Follow-Up Studies
• Gene Expression Regulation, Leukemic
• Humans
• Leukemia, Myeloid, Acute (metabolism, mortality, pathology)
• MDS1 and EVI1 Complex Locus Protein (biosynthesis)
• Male
• Middle Aged
• Multigene Family
• Neoplasm Proteins (biosynthesis)
• Nucleophosmin
• Proto-Oncogene Proteins (biosynthesis)
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-myc (biosynthesis)
• Survival Rate
• Trans-Activators
• Tumor Suppressor Proteins (biosynthesis)
• Up-Regulation