Achieved new goals in the research project funded by Fondazione Ginevra Caltagirone

Achieved new goals in the research project funded by Fondazione Ginevra Caltagirone

The objectives achieved during the last months of work of the Project funded by the Fondazione Ginevra Caltagirone always concern the scope relative to the deepening of the biological knowledge of acute myeloid leukemia of children.


And in fact continued the project of massive sequencing of the transcriptome of pediatric patients with acute myeloid leukemia ( AML ). As previously reported, the LAM are a heterogeneous group of malignancies arising from clonal proliferation of blood cells called myeloid cells . The disease strikes in Italy about 65 children a year and is still burdened by a decidedly ominous prognosis. The disease-free survival, in fact, children affected by LAM is now around 55-60 % at 5 years. The search for new biological markers that characterize this disease can not only help to better understand the behavior of the disease but also to trace the prognostic and develop new targeted drugs.


In detail , in continuation of the project undertaken with funding from the Fondazione Ginevra Caltagirone, was completed the massive sequencing of a particular variant of AML ( with deletion of the long arm of chromosome 5 ) which is associated with an unfavorable prognosis absolutely . We identified two new fusion transcripts , one of which has not previously been described , called RUNX1 - USP42 and PRDM16 - SKI , which can help a lot in understanding the biology and behavior of this type of leukemia


The results of this discovery were collected and summarized in a publication in a major scientific journal ( Masetti R , M Togni , Astolfi A, Pigazzi M , V Indio , Rivalta B , E Manara , Rutella S , Low G , Pession A, Locatelli F. Whole transcriptome sequencing of a pediatric case of de novo acute myeloid leukemia with del (5q ) Reveals RUNX1 - USP42 and PRDM16 - SKI fusion transcripts . Br J Haematol . 2014 Aug ; 166 ( 3 ) : 449-52.)


The process of knowledge of pediatric AML by massive sequencing of its genome has led during these years of the Project funded by the Foundation for important acquisitions . Have been identified mutations in genes that regulate cell proliferation and cell death in genes that code for enzymes that serve to divide the DNA , and others that are used to transcribe the DNA . Were collected results in major magazines like " Blood" ( Masetti R , Pigazzi M , Togni M , Astolfi A, V Indio , Manara And , Casadio R , Pession A, Basso G , Locatelli F. CBFA2T3 - GLIS2 fusion transcript is a novel feature common in pediatric , cytogenetically normal AML , not restricted to M7 FAB subtype . Blood . 2013 April 25 ; 121 ( 17 ) : 3469-72 ) and Oncotarget ( Masetti R , M Togni , Astolfi A, Pigazzi M , E Manara , Indio V , Rizzari C , Rutella S , Low G , Pession a, Locatelli F. DHH - RHEBL1 fusion transcript : a novel recurrent feature in the new landscape of pediatric CBFA2T3 - positive acute myeloid leukemia - GLIS2 . Oncotarget. 2013 Oct ; 4 ( 10 ) : 1712-20 ) .


These findings have been a valuable tool in the hands of clinicians to treat better and more successful children suffering from this serious disease . In fact one of these fusion genes recently identified , has been incorporated in the prognostic classification of children with AML who will be subjected to future national protocol for treatment of the Italian Association of Pediatric Hematology and Oncology .