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High Expression of Human Homologue of Murine Double Minute 4 and the Short Splicing Variant, HDM4-S, in Bone Marrow in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
- Source :
- Clinical Lymphoma Myeloma and Leukemia. 16:S30-S38
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- The human homologue of murine double minute 2 (HDM2) and HDM4 negatively regulate p53. HDM4 has not been assessed in acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We examined the expression of HDM4 and the short splicing variant, HDM4-S, in bone marrow samples obtained from 85 and 23 patients with AML and MDS, respectively, and 18 negative tumor staging bone marrow samples (used as the control). Immunohistochemical staining showed that HDM4 was overexpressed in 78 AML cases (92%) and 12 MDS cases (52%) compared with 1 stressed bone marrow sample (6%). Quantitative reverse transcriptase-polymerase chain reaction analysis of 8 AML and 11 low-grade (LG)-MDS cases confirmed that HDM4 and HDM4-S mRNA expression were also elevated in all AML cases. HDM4 and HDM4-S mRNA expression was elevated in 3 (27%) and 10 (91%) LG-MDS cases, respectively. HDM4 and HDM4-S mRNA levels were higher in those with AML than in those with LG-MDS. In leukemia cell lines, HEL and U937 predominantly expressed HDM4-S. In contrast, NALM6 expressed HDM4 and HDM4-S. Downregulation of HDM4 expression by treatment with small interfering RNA in NALM6 and HEL cells induced p21 expression but not increased apoptotic activity. Our results indicate that HDM4 is a potential therapeutic target in patients with AML or MDS.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Small interfering RNA
Pathology
Gene Expression
Cell Cycle Proteins
0302 clinical medicine
Bone Marrow
hemic and lymphatic diseases
RNA, Small Interfering
Child
Aged, 80 and over
Gene Expression Regulation, Leukemic
Nuclear Proteins
Myeloid leukemia
Hematology
Middle Aged
Immunohistochemistry
Leukemia, Myeloid, Acute
medicine.anatomical_structure
Oncology
Child, Preschool
030220 oncology & carcinogenesis
RNA splicing
Female
Adult
medicine.medical_specialty
Adolescent
Bone Marrow Cells
Young Adult
03 medical and health sciences
Downregulation and upregulation
Cell Line, Tumor
Proto-Oncogene Proteins
medicine
Humans
In patient
RNA, Messenger
Aged
Chromosome Aberrations
business.industry
Infant
Alternative Splicing
Genes, ras
030104 developmental biology
fms-Like Tyrosine Kinase 3
Apoptosis
Myelodysplastic Syndromes
Mutation
Cancer research
Bone marrow
business
Subjects
Details
- ISSN :
- 21522650
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Clinical Lymphoma Myeloma and Leukemia
- Accession number :
- edsair.doi.dedup.....6a2beec82bbd3d876659df7c35e3b17a