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These gene variants are on JAK2- Janus Kinase gene on the chromosome nine. Shai Izraeli, the M.D at Sheba Medical Center and colleagues say that these mutations are associated with the myeloproliferative disorders. However, these specific genetic variants which all affect an arginine residue that is highly conserved, R683, tend to differ from the alterations that are commonly seen as reported by the researchers.

How the research was conducted

These findings were reported after the bone marrow of 88 patients that were suffering from acute lymphoblastic leukemia linked with the Down’s syndrome was genetically analyzed as well as bone marrow from 109 patients suffering from childhood sporadic B- cell precursor acute lymphoblastic leukemia. Other subjects that participated in the study were 11 patients of Down’s syndrome that is associated with acute megakaryoblastic leukemia as well as 96 patients with the essential thrombocythemia negative disease for JAK2V617F mutation.

23 leukemia cancer cell lines were also analyzed by the researchers as well. According to the study findings, it became clear that 18 percent of children with Down’s syndrome with lymphoblastic leukemia also had the R683 locus alteration. Three of these changes were essentially missense variations where another amino acid were swapped for arginine and two of them involved complicated insertions and deletions immediately upstream from R683 locus according to the researchers.

The findings of the research and their implications

In contrast to this, among the 109 patients without Down’s syndrome but with acute sporadic B cell precursor leukemia, just one child aged 20 months had the R683 mutation. The researchers were amazed to see that the child actually had isochomosome at the chromosome 21. In this case, there was a loss of the short arm which was replaced with a copy identical to the long arm.

Down’s children having JAK2 mutations were quite younger on average when diagnosed compared to those with the wild type gene. In vitro, mutations that were caused by the cytokine independent growth for the mouse BaF3 cells suggested that these mutations are essentially gain of function cell drivers. This growth was incredibly sensitive to JAK inhibitor 1 inhibition when compared to cells that expressed Philadelphia chromosome.

What this implies is that the JAK inhibitors which some of them are used in clinical trials could be a very useful treatment for Down’s children with the mutations. JAK2 has a striking association with the two types of malignancy. This suggests that their location and nature could be crucial when it comes to dictating perturbation of the downstream signal cancer phenotype. The researchers also noted that the genome sequencing, together with other wide analyses of genome tend to lay bare genome for acute lymphoblastic leukemia and then allowed the identification of logical pathways where the disease was intervened therapeutically.