The relation between serum SETD2 And response to treatment in CML Patients on TKI

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease marked by chromosome translocation t(9;22) (q22;q11) that leads to the BCR-ABL1 fusion Gene. The resulting BCR-ABL1 fusion protein (p210), is a constitutively activated tyrosine kinase that drives the leukemic transformation of hematopoietic stem cells, and induces the progression of the disease from the early chronic phase (CP) to the blastic phase (BP) which fatally close the course of the disease (2–3) TKIs in the 2000s radically changed the fate of CML, since Imatinib (IM), before, Nilotinib (NIL), Dasatinib (DAS) or bosutinib (BOS), after, showed to be able to prevent the disease and Blastic transformation and significantly prolong the survival (4). CML is often divided into three phases based on clinical characteristics and laboratory findings. In the absence of intervention, CML typically begins in the chronic phase, and over the course of several years progresses to an accelerated phase and ultimately to a blast crisis. Blast crisis is the terminal phase of CML and clinically behaves like an acute leukemia. Drug treatment will usually stop this progression if started early. Some patients may already be in the accelerated phase or blast crisis by the time they are diagnosed.(5) SET domain containing 2 is an enzyme that in humans is encoded by the SETD2 gene. The SETD2 gene is located on the short arm of chromosome 3 and has been shown to play a tumor suppressor role in human. SET domain‐containing 2 (SETD2) is the major mammalian methyltransferase responsible for catalyzing the trimethylation of Histone 3 on lysine 3 (H3K36me3). Mutations of SETD2 have been found in various types