- Researchers from St
Jude's Children's research hospital have identified gene signature for certain
pediatric acute lymphoblastic leukemia subtypes.
in DUX 4 gene leads to lowered production of the transcription factor ERG that
leads to the development of Acute Lymphoblastic Leukemia (ALL).
genetic marker can be used to identify high risk patients and also provide new
The changes in the genes
that lead to the development B precursor acute lymphoblastic leukemia
, one of the most common forms of cancer in children,
have been identified by researchers from St Jude's Children's Research
Hospital, University of Washington's Pediatric Cancer Genome Project and The
Children's Oncology group.
The genetic alterations
in DUX4 and ERG, which are transcription factors and which have been found to
affect other critical genes found in the human blood cells of patients with acute
lymphoblastic leukemia. There has been poor understanding of the
genetic changes that take place in this form of cancer which has been the main
reason behind the study.
‘Key genetic signature that leads to the development of acute lymphoblastic leukemia in children could be a marker for identification and provide drug targets.’
Dr Charles Mullighan
from the Department of Pathology St Jude said "Our work is motivated by a
lack of information on the genetic basis of many B-ALL cases. We discovered a
distinct gene pattern in blood samples from some of the patients in our study
and wanted to determine the underlying molecular events behind this
Distinctive Genetic Profile
Associated with Acute Lymphoblastic Leukemia
The researchers studied
1913 patients with B precursor lymphoblastic
leukemia which included children, young adults and adolescents. 7.6%
of these patients had a distinctive genetic profile that prompted further
The Chief of the
Division of Oncology at the Philadelphia's Children's Hospital and co-author Dr
Stephen Hunger, "These findings explain the genetic defects that underlie
a relatively common subset of B-ALL that was not fully understood until the
DUX4 abnormalities were discovered. These results underscore that there is still
more to be learned about the genetic changes
, and that this knowledge
can help refine treatment for patients,"
of Development of Leukemia
Dr Mullighan added
"Our work revealed that in this type of B-ALL there is a sequence of
molecular events that involves the interplay of two transcription
The sequencing studies
carried out by the researchers revealed the following:
- In the subtypes of ALL, there was
a rearrangement of the transcription factors gene DUX4.
resulted in an increased expression of the gene
- DUX4 binds
to the gene that is responsible for the transcription factor ERG
lead to a decreased production of ERG
- The lowered level of
ERG was due to a deletion of a part of the gene or due to the secretion of
another form of ERG, ERGalt
In both the incidences,
where the level of ERG was lowered, it leads to the development of leukemia.
The Chair of the Department
of Computational Biology at St Jude's Dr Jinghui Zhang said "The discovery
of the connection between DUX4 fusion and the aberrant ERG isoform required
integrating whole-genome sequencing, RNA-seq and ChIP-seq data using novel
computational approaches that we developed."
The genetic structure of
this particular variant of BLL is available in a tool that has been developed
by the researchers from St Jude that is used to detail cancer mutations in
Dr Li Ding who is the
assistant director of The McDonnell Genome Institute and director of
computational biology at the Washington University School of Medicine's
Division of Oncology noted: "Our data reveal that a genetic rearrangement
of DUX4 is present in all cases for patients with the distinct gene expression
profile that was identified in our study. The genetic rearrangement of DUX4 is
a clonal event that is acquired early in the development of leukemia
Acute Lymphoblastic Leukemia
In this type of cancer,
the body makes a lot of immature white blood cells. The cancer affects the red
blood cells, white blood cells as well as the platelets. In children, the
symptoms include fever and bruising.
leukemia is caused due to certain genetic abnormalities and in adults, previous
treatments for cancer have also been implicated.
The identification of
the abnormality in the DUX4 gene will aid in better identification of
high risk patients using genetic
testing and provide new targets for drug therapy.
- Childhood Acute Lymphoblastic Leukemia
Treatment - (https:www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq)
- Acute lymphoblastic leukaemia (ALL) in
children - (http://www.macmillan.org.uk/cancerinformation/cancertypes/childrenscancers/typesofchildrenscancers/acutelymphoblasticleukaemia.aspx)