Dr. Ilaria Pagani - CML - Chronic myeloid leukemia

Dr. Ilaria S Pagani joined the Leukaemia Research Group at SAHMRI in July 2014, developing two projects on chronic myeloid leukaemia (CML). 
CML is a myeloproliferative disease characterize by the t(9;22)(q34;q11) balanced reciprocal translocation. The hallmark of the CML is the BCR/ABL1 fusion gene on Philadelphia chromosome (Ph), which encodes for a constitutively active protein tyrosine kinase (TK) that confers proliferative advantages to the Ph-positive clone. Tyrosine kinase inhibitors (TKIs) dramatically improved the survival of chronic myeloid leukaemia (CML) patients. TK inhibitors (TKIs) have revolutionized the management of the CML, providing target therapy for patients. Despite the success of TKIs in long-term survival, variations in treatment outcome suggest a possible secondary mechanism of resistance due to the persistence of a pre-existing clone that had acquired additional genetic lesions. The first project is the characterization of the genomic landscape of mitochondrial (mt) DNA mutations in CML by next generation sequencing techniques, identifying a sub-group of patients that respond well to therapy. Next goal will be to determine whether mtDNA mutations influence the susceptibility of CML cells to undergo apoptosis in response to tyrosine kinase inhibition. 
Even if 50% of patients who achieved a deep molecular response and maintain it for 2 years can stop TKIs without relapsing, about half of patients experience molecular relapse. The second project is the investigation of whether lineage and proliferative potential of residual leukaemia are key determinants of treatment free remission after stopping therapy in comparison with relapse patients.
Extract of SAHMRI