IMMOBILIZED KINASE ACTIVITY BIOSENSORS FOR ABL KINASE IN CHRONIC MYELOID LEUKEMIA

Chronic Myelogenous Leukemia (CML) is a blood cancer that affects each yearmore than 4500 patients in USA and more than 7500 in Europe. CML is caused byan acquired chromosomal rearrangement that results in the creation of BCR-ABL1, an abnormally active kinase. The uncontrolled activity of this kinasedetermines the accumulation of immature myeloid cells and the reduction of redblood cells and platelets in the blood stream. These changes compromise thefunction of immune system, oxygen delivery and coagulation. This diseaseremains often silent for many years in a so-called chronic phase (CP), but if leftuntreated, it proceeds to the more aggressive and least treatable accelerating(AP) and blastic phases (BP). Intervening with an effective therapeutic regimenin the shortest time possible is therefore of paramount importance.The standard clinical approach prescribes the detection of BCR-ABL1 kinasedomain mutations only in patients with an inadequate initial response to TKIs(primary resistance). The lack of initial response can be detected only after aminimum of 3-12 months from the diagnosis.The ability to understand how patients respond to drugs at diagnosis with asimple analysis of peripheral blood would help clinicians to prescribe morepatient-tailored treatments decreasing the insurgence of future drug resistance.The test assay we are proposing is based on an immobilized syntheticallyoptimized peptide with a high specificity for BCR-ABL1. The test uses antibodiesto detect the occurred peptide phosphorylation from appropriately preparedperipheral blood or bone marrow cell lysates.