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The role of CTCF and cohesin in high hyperdiploid childhood acute lymphoblastic leukemia

Dias Moura, Larissa Helena (2018) MOBN03 20172
Degree Projects in Molecular Biology
Popular Abstract
Chromosome defects in high hyperdiploid childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a type of blood cancer that affects both adults and children. While human cells normally harbor 46 chromosomes, the leukemic cells of the high hyperdiploid subgroup (HeH) of childhood ALL presents 51-67 chromosomes, where the extra chromosomes are generally X, 4, 6, 10, 14, 17, 18 and 21. The HeH ALL subgroup affects children mostly between 2-4 years old, representing 25-30% of all childhood ALL, and it is associated with good prognosis. The CTCF protein and the cohesin protein complex are important during cell division and chromosome structure regulation. As it remains unclear how the extra chromosomes arise or how the... (More)
Chromosome defects in high hyperdiploid childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a type of blood cancer that affects both adults and children. While human cells normally harbor 46 chromosomes, the leukemic cells of the high hyperdiploid subgroup (HeH) of childhood ALL presents 51-67 chromosomes, where the extra chromosomes are generally X, 4, 6, 10, 14, 17, 18 and 21. The HeH ALL subgroup affects children mostly between 2-4 years old, representing 25-30% of all childhood ALL, and it is associated with good prognosis. The CTCF protein and the cohesin protein complex are important during cell division and chromosome structure regulation. As it remains unclear how the extra chromosomes arise or how the induction and development of this type of leukemia occurs, one possibility is that abnormal gene regulation involving CTCF and cohesin could affect these processes.

HeH ALL patients were compared to ETV6/RUNX1-positive ALL cases, another subgroup of childhood ALL that also presents a good outcome. A total of 48 HeH and 37 ETV6/RUNX1-positive ALL cases were included in this study. By using molecular techniques and chromosome analysis, we investigated the frequency of mutations in CTCF and cohesin in HeH cases. It is commonly said that chromosomes in HeH ALL are very short and ”ugly”, with a fuzzy shape. Thus, we performed chromosome studies to determine if HeH cases presented chromosome defects or poor chromosome morphology when compared to other subgroups of ALL.

The chromosome studies showed that 85% of the HeH cases presented chromosome defects, where 15% of the HeH cases were severely affected. It was also confirmed that hyperdiploid cells have the poorest chromosome morphology compared with ETV6/RUNX1-positive cells. However, no clear correlation was observed between gene dysregulation and chromosome defects.

A fusion between two genes, caused by a chromosome translocation, was detected in one patient; one of the involved genes is part of the cohesin complex, and this case presented 40% of chromosome defects. Deletions in genes that are relevant in HeH ALL were also confirmed in two other patients by molecular techniques.

Ultimately, our findings suggest that chromosome defects and poor chromosome morphology are important features of the chromosome pattern in high hyperdiploid childhood ALL. We believe that by having a better understanding of how chromosome and genomic aberrations function in HeH ALL, new targets to improve leukemia treatment may be discovered.

Master’s Degree Project in Molecular Biology, Molecular Genetics and Biotechnology 120 credits 2018
Department of Biology, Lund University

Advisor: Kajsa Paulsson
Advisors Unit/Department: Section of Aneuploidy in Cancer, Division of Clinical Genetics (Less)
Please use this url to cite or link to this publication:
author
Dias Moura, Larissa Helena
supervisor
organization
course
MOBN03 20172
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8952132
date added to LUP
2018-06-21 11:08:10
date last changed
2018-06-21 11:08:10
@misc{8952132,
  author       = {{Dias Moura, Larissa Helena}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The role of CTCF and cohesin in high hyperdiploid childhood acute lymphoblastic leukemia}},
  year         = {{2018}},
}