CASC5 Gene Expression Changes Correlate with Targeted Mutations in Leukemia

• Published in: Molecular biology (New York) Vol. 55; no. 1; pp. 121 - 132
• Main Authors: Bogdanov, K. V., Merzlikina, O. V., Mirolyubova, Y. V., Girshova, L. L., Lomaia, E. G., Zaritskey, A. Y.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2021; Springer Nature B.V
• Subjects: Acute myeloid leukemia; Anaphase; Aneuploidy; Biochemistry; Biomedical and Life Sciences; Bone marrow; Bone marrow transplantation; Chemotherapy; Chromatids; Chromosomes; Gene expression; Human Genetics; Leukemia; Leukemogenesis; Life Sciences; Microtubules; Mitosis; Molecular Cell Biology; Mutation; Myc protein; Myeloid leukemia; Sister chromatids; Solid tumors; Tumorigenesis; oncogenes; leukemia; mutations; expression; regulation
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893321010027

Dysfunction of genes that control mitosis and are responsible for the correct segregation of sister chromatids in anaphase is often accompanied by aneuploidy, which is frequently detected in leukemia. One of the components of the kinetochore complex, namely, the AF15q14/KNL1/CASC5 protein, is an important factor ensuring the correct binding of the pericentromeric region of chromosomes with the spindle microtubules. As shown recently, in some leukemias, the gene of this protein can be involved in the generation of the chromosomal translocation t(11;15)(q23;q14) or a variant of the chimeric
MLL-AF15Q14
oncogene, which serves as a biomarker of poor prognosis. Despite the implication of mRNA of the
CASC5
gene in oncogenesis of solid tumors, expression of this gene in hematopoietic neoplasms has not been studied. We analyzed expression levels of the
CASC5
gene and the nearest regulatory genes, including
WT1
,
APOBEC3A
(
A3A
), and
N-MYC
. A pronounced decrease in
CASC5
expression in bone marrow cells of primary leukemia patients compared with healthy donors was found. It was also shown that reduced expression of the
CASC5
gene correlates with the detection of targeted mutations in patients composed two prognostic subgroups (favorable, unfavorable) with a significance level (
p
<0.05). It was noted that the change in the expression level of the
CASC5
gene in acute myeloid leukemia is associated with overexpression of the genes
WT1
,
A3A
, and in some cases
N-MYC
and
SPT16
, which is consistent with the resistance to chemotherapy and leukemia progression. However, the question of which regulatory gene initiates leukemogenesis remains open.