327mutation leading to a tyrosine kinase deregulation would make a suitable target for
the development of specifi c therapies. QIAGEN Marseille has worldwide exclusive
IP rights to a test based on mutations in the JAK2 gene.
The advent of high-throughput NGS technologies, which are revolutionizing
genomics and transcriptomics by providing a single base resolution tool for a uni-
fi ed deep analysis of diseases complexity, enable fast and cost-effi cient fi ne-scale
assessment of the genetic variability hidden within cohorts of patients affected by
the same leukemia. That being so, by potentially highlighting inter-individual dif-
ferences that may play a role in the differential success of diverse therapeutic inter-
ventions, they promise to be crucial for selecting the most appropriate medical
treatments.
The NGS-PTL (personalized therapy of leukemia) project aims at developing a
European platform of scientists for improving outcomes for therapeutic interven-
tions on acute and chronic leukemias and at developing strategies to personalize
treatments and tailor therapies to different groups of leukemia patients, with the
main goal of optimizing their effi cacy and safety through a deeper understanding of
the infl uence of genomic alterations on leukemias pathogenesis and treatment
response. The systematic whole exome/transcriptome studies on clinically well-
characterized leukemia patients scheduled within the project are therefore expected
to help the identifi cation of novel prognostic biomarkers for acute and chronic leu-
kemias, as well as of molecular biomarkers and/or genome-wide profi les for the
assessment of minimal residual disease.
Personalized Management of Acute Lymphoblastic Leukemia
Progress in the molecular classifi cation of acute lymphoblastic leukemia (ALL)
with the use of DNA microarrays combined with methods to assess the functional
signifi cance of newly discovered genes or through proteomic techniques, will lead
to the identifi cation of targets for specifi c treatments. Imatinib mesylate, introduced
for the treatment of BCR-ABL-positive CML, inhibits the BCR-ABL fusion protein
and other constitutively active tyrosine kinases and induces transient remissions of
BCR-ABL-positive ALL as well as partial responses in other cancers, is the fore-
runner of a new generation of molecularly targeted anticancer drugs. Other poten-
tially useful agents that are under development include inhibitors of FLT-3 tyrosine
kinases for use against leukemias characterized by activating mutations of this
kinase and inhibitors of histone deacetylase for leukemias such as TEL-AML1-
positive ALL. Further refi nements in the molecular classifi cation of ALL, together
with the identifi cation of genetic features that affect the effi cacy and toxicity of
antileukemic therapy, will provide unique opportunities to devise treatment plans
for individual patients and thus to realize the elusive goal of cure in all patients,
regardless of their presenting characteristics. ALL is treated with a cocktail of che-
motherapeutic agents that include 6-mercaptopurine, 6-thioguanine and azathiopu-
rine. These drugs are broken down by the (TPMT). Those lacking functional TPMT
can suffer severe toxicity or death but these patients can be treated with doses that
Personalized Management of Cancers of Various Organs