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Loss of heterozygosity in childhood de novo acute myelogenous leukemia
- Source :
- Blood. 98:1188-1194
- Publication Year :
- 2001
- Publisher :
- American Society of Hematology, 2001.
-
Abstract
- A genome-wide screening for loss of heterozygosity (LOH), a marker for possible involvement of tumor suppressor genes, was conducted in 53 children with de novo acute myelogenous leukemia (AML). A total of 177 highly polymorphic microsatellite repeat markers were used in locus-specific polymerase chain reactions. This comprehensive allelotyping employed flow-sorted cells from diagnostic samples and whole-genome amplification of DNA from small, highly purified samples. Nineteen regions of allelic loss in 17 patients (32%) were detected on chromosome arms 1q, 3q, 5q, 7q (n = 2), 9q (n = 4), 11p (n = 2), 12p (n = 3), 13q (n = 2), 16q, 19q, and Y. The study revealed a degree of allelic loss underestimated by routine cytogenetic analysis, which failed to detect 9 of these LOH events. There was no evidence of LOH by intragenic markers for p53, Nf1, or CBFA2/AML1. Most lymphocytes lacked the deletions, which were detected only in the leukemic myeloid blast population. Analysis of patients' clinical and biologic characteristics indicated that the presence of LOH was associated with a white blood cell count of 20 x 10(9)/L or higher but was not correlated with a shorter overall survival. The relatively low rate of LOH observed in this study compared with findings in solid tumors and in pediatric acute lymphoblastic leukemia and adult AML suggests that tumor suppressor genes are either infrequently involved in the development of pediatric de novo AML or are inactivated by such means as methylation and point mutations. Additional study is needed to determine whether these regions of LOH harbor tumor suppressor genes and whether specific regions of LOH correlate with clinical characteristics. (Blood. 2001;98:1188-1194)
- Subjects :
- Male
medicine.medical_specialty
Myeloid
Adolescent
Tumor suppressor gene
Immunology
Population
Loss of Heterozygosity
Biology
medicine.disease_cause
Biochemistry
Loss of heterozygosity
Leukocyte Count
Myelogenous
medicine
Humans
Genes, Tumor Suppressor
Child
education
neoplasms
education.field_of_study
Infant, Newborn
Cytogenetics
Infant
Cell Biology
Hematology
Flow Cytometry
Prognosis
medicine.disease
Leukemia, Myeloid, Acute
Leukemia
medicine.anatomical_structure
Child, Preschool
Cytogenetic Analysis
Cancer research
Female
Carcinogenesis
Microsatellite Repeats
Subjects
Details
- ISSN :
- 15280020, 00064971, and 11881194
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....1cd0a66093f6093c45897de917fcef73