In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients.
Expression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia.
Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.
Emerging data recently suggested that molecular study of the mutations of NPM1, FLT3, MLL, and CEBPalpha and alterations in expression levels of BAALC, MN1, and ERG may identify poor-risk patients with NC AML.
Although overexpression of the brain and acute leukemia, cytoplasmic (<i>BAALC</i>) gene is associated with primary resistant disease and shorter relapse-free, disease-free, and overall survival in different subsets of acute myeloid leukemia (AML), little is known about its clinical impact in acute promyelocytic leukemia (APL).
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.
High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations.
Newly diagnosed AML patients with normal karyotype who were treated by the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed in terms of their BAALC expression levels (n = 29), BAALC isoforms (n = 29), and CEBPA mutations (n = 49).
The association of high BAALC expression with the T allele and its correlations with RUNX1 expresser status are shown in vivo in a test set (n = 253) and validation set (n = 105) of samples from cytogenetically normal AML patients from different populations.
RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD-NPM1) and BAALC and EVI1 expression.
To identify BAALC-associated genes that give insights into its functional role in chemotherapy resistance, gene expression signatures differentiating high from low BAALC expressers were generated from normal CD34(+) progenitors, T-acute lymphoblastic leukemia (T-ALL) and AML samples.
Four prognostic biomarkers-the internal tandem duplication and point mutations in the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA gene, and overexpression of the BAALC gene-have been found to predict outcome in patients with AML and normal cytogenetics.
Furthermore, expression levels of several genes affiliated with drug resistance or indicative of poor prognosis AML (BAALC, CD34, PRG2, TSPAN7) are affected by AML1/MTG8 depletion.
Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT.
Recent studies have shown that high BAALC expression predicts an adverse prognosis and may define an important risk factor in acute myeloid leukemia patients with normal karyotype.
Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML).
Older acute myeloid leukemia (AML) patients with high expression of both miR-3151 and the BAALC mRNA transcript have a low survival prognosis, and miR-3151 and BAALC expression is associated with poor survival independently of each other.
Thus low MDR1/low BAALC expression identifies a subgroup of intermediate cytogenetic risk AML patients with a remarkably good long-term outcome achieved by chemotherapy alone.