Related Experiment Video
Updated: May 23, 2026
10:21
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Heritable polymorphism predisposes to high BAALC expression in acute myeloid leukemia
Ann-Kathrin Eisfeld1, Guido Marcucci, Sandya Liyanarachchi
1The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Summary
A specific gene variant (T allele of rs62527607) drives overexpression of the brain and acute leukemia, cytoplasmic (BAALC) gene, potentially increasing acute myeloid leukemia risk. This genetic feature may aid personalized medicine approaches.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- The brain and acute leukemia, cytoplasmic (BAALC) gene is overexpressed in various cancers, including acute myeloid leukemia (AML), and linked to poor patient outcomes.
- The mechanisms causing BAALC overexpression and its oncogenic role remain largely unknown.
- A heritable genetic factor influencing BAALC expression in an allele-specific manner was hypothesized.
Purpose of the Study:
- To investigate the genetic basis for BAALC overexpression.
- To identify specific genetic variants associated with BAALC expression levels.
- To elucidate the functional consequences of these variants in leukemogenesis.
Main Methods:
- Sequencing of the BAALC genomic region to identify single nucleotide polymorphisms (SNPs).
- Association studies testing SNPs against BAALC expression levels in patient cohorts.
- In vitro luciferase reporter assays and electrophoretic mobility shift assays (EMSA) to confirm functional mechanisms.
- In vivo validation in independent AML patient cohorts.
Main Results:
- The T allele of SNP rs62527607 was significantly associated with higher BAALC expression.
- This T allele creates a binding site for the RUNX1 transcription factor in the BAALC promoter.
- In vitro and in vivo experiments confirmed the functional and correlational link between the T allele, RUNX1, and BAALC overexpression in AML.
- High BAALC expression and the T allele were correlated with RUNX1 expresser status in cytogenetically normal AML patients.
Conclusions:
- A heritable genetic variant (rs62527607 T allele) predisposes to BAALC oncogene overexpression.
- This mechanism contributes to acute myeloid leukemia pathogenesis.
- Genomic variants may serve as biomarkers for personalized medicine in oncology.
Related Concept Videos
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:49Multiple Allele Traits
The Concept of Multiple Allelism
01:11Genetic Lingo
Overview
01:27Disorders of Leukocytes
Leukocyte disorders can lead to either leukopenia, characterized by an abnormally low leukocyte count, or leukocytosis, marked by a very high leukocyte number.
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune system...
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune system...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...