Saturday, May 19, 2012

Friday's Facts 051812: DS and Leukemia

Individuals with Down syndrome have a 15 to 20 times greater risk of developing leukemia.

The majority of cases are categorized as acute megakaryoblastic leukemia (AMkL), which tends to occur in the first three years of life; thankfully, there is a high cure rate.

A transient form of leukemia is also seen in newborns with Down syndrome, disappearing spontaneously during the first two to three months of life.

One in every 95 children with Down syndrome develops leukemia, compared with one in every 2000 children without Down syndrome.

It appears that the extra genetic material found on chromosome 21 also may cause stem cells to proliferate before they have developed to maturity, creating “blast cells,” and thus, leukemia.

Children with Down syndrome are usually diagnosed with one of the two major forms of leukemia -- ALL (acute lymphoblastic leukemia) and AML (acute myeloid leukemia) -- in about the same proportion as all other children.

Compared to most children with AML, children who also have Down syndrome respond to treatment better, and have survival rates as high as 85%, compared with 50-55% for the others.

     For children with Down syndrome, leukemia treatment is more successful than for other kids. It's likely due to a genetic mutation found only in Down syndrome children, new research shows. However, the same mutation also increases the kids' leukemia risk.

     Children's cancer researchers have consistently reported the pattern. A specific type of acute myeloid leukemia (AML) called acute megakaryocytic leukemia (AMkL) is the most common type of AML in young children with Down syndrome.

     Recent studies have identified a genetic mutation in virtually all Down syndrome children who have AMkL. Non-Down syndrome kids with AML don't have this mutation. The mutation, known as the 40-kDa GATA1 protein, may be responsible for the survival difference.

     The GATA1 mutation seems to contribute to the Down syndrome kids' greater sensitivity to a specific cancer fighting drug, called cytosine arabinoside, which is used in treating AMkL.

     Cells with the normal GATA1 protein were 8 to 17 times less sensitive to the chemotherapy drug.  They were also 15 to 25 times less sensitive to gemcitabine, another leukemia drug.

     Tests of cells taken from 16 newly diagnosed Down syndrome children (including 12 AMkL patients) and 56 non-Down syndrome children with AML showed that 14 of 16 Down syndrome kids had the GATA1 mutation.

     This GATA1 mutation is a double-edged sword. It may increase a child's risk for leukemia, but it may also contribute to the high survival and low relapse rates of this unique group of Down syndrome patients.


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