2009.08.31 – Genetic Link Between Leukemia And Down’s Syndrome


By urgesboard | August 31, 2009

Researchers are closer to developing drugs to usage of acute lymphoblastic
leukemia (ALL) after identifying mutations in the JAK2
gene tangled in Down’s syndrome, which is associated with this form of
leukemia. Dr Shai Izraeli (Sheba Medical Nave, Ramat Gan,
Israel) and colleagues explain their scrutinize in an article published
early online and in an upcoming copy of The Lancet.

A cancer of the blood or bone marrow, leukemia is a disease
characterized by aberrant reproduction of leukocytes, or white blood
cells. Down’s syndrome is a genetic disorder that occurs when
a human has a third facsimile of chromosome 21 rather than the normal 23
pairs of chromosomes. Not only does Down’s syndrome leave children with
impaired cognitive talent and physical growth, but the condition also
results in a 20-times increased risk of developing acute leukemia,
including ALL. Since mutations of the gene JAK2
have on the agenda c trick been linked to cancers that affect other types of white blood stall
(myeloproliferative) disorders, Dr Izraeli and colleagues hypothesized
that mutations of JAK2 are a common molecular effect come what may
found in Down’s syndrome-related ALL.

The tests required bone marrow samples from patients with Down’s
syndrome-interconnected ALL. Of 87 patients who met the necessary
criteria, 18% (16) had somatically (spontaneous, not
inherited) acquired JAK2 mutations. In addition,
the researchers set that children with a JAK2
modifying were 4.1 years younger at ALL diagnosis than those children
who did not have the evolution – 4.5 years vs. 8.6 years. The
study revealed five mutations (alleles) that each affected a distinct
amino-acid residuum in the protein that the gene encoded, called R683.

Dr Izraeli and colleagues conclude that there is a specific association
between the event of conditions such as ALL and somatic mutation
in the JAK2 gene. They compose: “Somatically acquired
R683 JAK2 mutations define a clear canny
lymphoblastic leukaemia subgroup that is uniquely associated with
Down’s Syndrome. JAK2 inhibitors could be beneficial
proper for treatment of this leukaemia.”

Dr Charles G Mullighan (St Jude Children’s Research Hospital, Memphis,
TN, USA) writes in an accompanying article hither the successful
progress that has been made in resequencing entire
genomes leukemia and other tumors. Mullighan writes: “These
approaches, coupled with genome-wide analyses of alterations to DNA
copy tally and epigenetic phenomena, will ballade bare the genome of acute
lymphoblastic leukaemia, and allow us to identify logical pathways to go to
therapeutic intervention in this murrain.”

Mutations of JAK2 in pointed
lymphoblastic leukaemias associated with Down’s syndrome
Dani Bercovich, Ithamar Ganmore, Linda M Scott, Gilad
Wainreb, Yehudit Birger, Arava Elimelech, Chen Shochat, Giovanni
Cazzaniga, Andrea Biondi, Giuseppe Basso, Gunnar Cario, Martin
Schrappe, Martin Stanulla, Sabine Strehl, Oskar A Haas, Georg Mann,
Vera Binder, Arndt Borkhardt, Helena Kempski, Jan Trka, Bella Bielorei,
Smadar Avigad, Batia Stark, Owen Smith, Nicole Dastugue, Jean-Pierre
Bourquin, Nir Ben Tal, Anthony R Green, Shai Izraeli
The Lancet (2008).